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Notum deacylates Wnt proteins to suppress signalling activity.

<div class='caption-title'>Notum specifically inhibits Wnt signalling</div>
<div class='caption-title'>Notum requires the GAGs of glypicans to inhibit Wingless signalling</div>
<div class='caption-title'>hNotum structure and GAG binding</div>
Kakugawa S, Langton PF, Zebisch M, Howell S, Chang TH, Liu Y, Feizi T, Bineva G, O'Reilly N, Snijders AP, Jones EY, Vincent JP
OpenAccess logo Nature 519 187-192 (2015)
Related entries: 4uyw, 4uyz, 4uz1, 4uz5, 4uz6, 4uz7, 4uz9, 4uza, 4uzj, 4uzk, 4uzl, 4uzq, 4wbh

Cited: 237 times
EuropePMC logo PMID: 25731175

Abstract

Signalling by Wnt proteins is finely balanced to ensure normal development and tissue homeostasis while avoiding diseases such as cancer. This is achieved in part by Notum, a highly conserved secreted feedback antagonist. Notum has been thought to act as a phospholipase, shedding glypicans and associated Wnt proteins from the cell surface. However, this view fails to explain specificity, as glypicans bind many extracellular ligands. Here we provide genetic evidence in Drosophila that Notum requires glypicans to suppress Wnt signalling, but does not cleave their glycophosphatidylinositol anchor. Structural analyses reveal glycosaminoglycan binding sites on Notum, which probably help Notum to co-localize with Wnt proteins. They also identify, at the active site of human and Drosophila Notum, a large hydrophobic pocket that accommodates palmitoleate. Kinetic and mass spectrometric analyses of human proteins show that Notum is a carboxylesterase that removes an essential palmitoleate moiety from Wnt proteins and thus constitutes the first known extracellular protein deacylase.

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  2. The structural biology of canonical Wnt signalling. Agostino M, Pohl SÖ. Biochem Soc Trans 48 1765-1780 (2020)

Articles - 4uyu mentioned but not cited (7)

  1. Notum deacylates Wnt proteins to suppress signalling activity. Kakugawa S, Langton PF, Zebisch M, Howell S, Chang TH, Liu Y, Feizi T, Bineva G, O'Reilly N, Snijders AP, Jones EY, Vincent JP. Nature 519 187-192 (2015)
  2. Plant pectin acetylesterase structure and function: new insights from bioinformatic analysis. Philippe F, Pelloux J, Rayon C. BMC Genomics 18 456 (2017)
  3. Carboxylesterase Notum Is a Druggable Target to Modulate Wnt Signaling. Bayle ED, Svensson F, Atkinson BN, Steadman D, Willis NJ, Woodward HL, Whiting P, Vincent JP, Fish PV. J Med Chem 64 4289-4311 (2021)
  4. Structural characterization of melatonin as an inhibitor of the Wnt deacylase Notum. Zhao Y, Ren J, Hillier J, Jones M, Lu W, Jones EY. J Pineal Res 68 e12630 (2020)
  5. Notum deacylates octanoylated ghrelin. Zhao Y, Schuhmacher LN, Roberts M, Kakugawa S, Bineva-Todd G, Howell S, O'Reilly N, Perret C, Snijders AP, Vincent JP, Jones EY. Mol Metab 49 101201 (2021)
  6. Caffeine inhibits Notum activity by binding at the catalytic pocket. Zhao Y, Ren J, Hillier J, Lu W, Jones EY. Commun Biol 3 555 (2020)
  7. Structural Insights into Notum Covalent Inhibition. Zhao Y, Svensson F, Steadman D, Frew S, Monaghan A, Bictash M, Moreira T, Chalk R, Lu W, Fish PV, Jones EY. J Med Chem 64 11354-11363 (2021)


Reviews citing this publication (78)

  1. Wnt/β-Catenin Signaling, Disease, and Emerging Therapeutic Modalities. Nusse R, Clevers H. Cell 169 985-999 (2017)
  2. Wnt/β-catenin signalling: function, biological mechanisms, and therapeutic opportunities. Liu J, Xiao Q, Xiao J, Niu C, Li Y, Zhang X, Zhou Z, Shu G, Yin G. Signal Transduct Target Ther 7 3 (2022)
  3. Wnt signaling in development and tissue homeostasis. Steinhart Z, Angers S. Development 145 dev146589 (2018)
  4. Wnt/β-catenin signaling in cancers and targeted therapies. Yu F, Yu C, Li F, Zuo Y, Wang Y, Yao L, Wu C, Wang C, Ye L. Signal Transduct Target Ther 6 307 (2021)
  5. Wnt signaling in breast cancer: biological mechanisms, challenges and opportunities. Xu X, Zhang M, Xu F, Jiang S. Mol Cancer 19 165 (2020)
  6. Targeting Wnt signaling in colorectal cancer. A Review in the Theme: Cell Signaling: Proteins, Pathways and Mechanisms. Novellasdemunt L, Antas P, Li VS. Am J Physiol Cell Physiol 309 C511-21 (2015)
  7. WNT Signaling in Cardiac and Vascular Disease. Foulquier S, Daskalopoulos EP, Lluri G, Hermans KCM, Deb A, Blankesteijn WM. Pharmacol Rev 70 68-141 (2018)
  8. Glypican-3: A promising biomarker for hepatocellular carcinoma diagnosis and treatment. Zhou F, Shang W, Yu X, Tian J. Med Res Rev 38 741-767 (2018)
  9. Fatty acylation of proteins: The long and the short of it. Resh MD. Prog Lipid Res 63 120-131 (2016)
  10. WNT Signaling in Cancer Immunosurveillance. Galluzzi L, Spranger S, Fuchs E, López-Soto A. Trends Cell Biol 29 44-65 (2019)
  11. microRNA regulation of Wnt signaling pathways in development and disease. Song JL, Nigam P, Tektas SS, Selva E. Cell Signal 27 1380-1391 (2015)
  12. Next-Generation Cancer Immunotherapy Targeting Glypican-3. Shimizu Y, Suzuki T, Yoshikawa T, Endo I, Nakatsura T. Front Oncol 9 248 (2019)
  13. Integrity of the Intestinal Barrier: The Involvement of Epithelial Cells and Microbiota-A Mutual Relationship. Gieryńska M, Szulc-Dąbrowska L, Struzik J, Mielcarska MB, Gregorczyk-Zboroch KP. Animals (Basel) 12 145 (2022)
  14. The Wnt signaling pathway: a potential therapeutic target against cancer. Ghosh N, Hossain U, Mandal A, Sil PC. Ann N Y Acad Sci 1443 54-74 (2019)
  15. Glypican 3-Targeted Therapy in Hepatocellular Carcinoma. Nishida T, Kataoka H. Cancers (Basel) 11 E1339 (2019)
  16. Structural Perspectives on Axon Guidance. Seiradake E, Jones EY, Klein R. Annu Rev Cell Dev Biol 32 577-608 (2016)
  17. Understanding cell-cell communication and signaling in the colorectal cancer microenvironment. AlMusawi S, Ahmed M, Nateri AS. Clin Transl Med 11 e308 (2021)
  18. Mechanisms of Wnt signaling and control. Grainger S, Willert K. Wiley Interdiscip Rev Syst Biol Med 10 e1422 (2018)
  19. New Insights Into Monogenic Causes of Osteoporosis. Mäkitie RE, Costantini A, Kämpe A, Alm JJ, Mäkitie O. Front Endocrinol (Lausanne) 10 70 (2019)
  20. GPI-AP release in cellular, developmental, and reproductive biology. Fujihara Y, Ikawa M. J Lipid Res 57 538-545 (2016)
  21. Functions of the WNT Signaling Network in Shaping Host Responses to Infection. Ljungberg JK, Kling JC, Tran TT, Blumenthal A. Front Immunol 10 2521 (2019)
  22. Wnt Signaling Cascades and the Roles of Syndecan Proteoglycans. Pataki CA, Couchman JR, Brábek J. J Histochem Cytochem 63 465-480 (2015)
  23. Role of the Wnt signaling molecules in the tooth. Tamura M, Nemoto E. Jpn Dent Sci Rev 52 75-83 (2016)
  24. Chemoresistance and targeting of growth factors/cytokines signalling pathways: towards the development of effective therapeutic strategy for endometrial cancer. Guo F, Zhang H, Jia Z, Cui M, Tian J. Am J Cancer Res 8 1317-1331 (2018)
  25. Go ahead, grow a head! A planarian's guide to anterior regeneration. Owlarn S, Bartscherer K. Regeneration (Oxf) 3 139-155 (2016)
  26. Peptide Lipidation - A Synthetic Strategy to Afford Peptide Based Therapeutics. Kowalczyk R, Harris PWR, Williams GM, Yang SH, Brimble MA. Adv Exp Med Biol 1030 185-227 (2017)
  27. The Emerging Mechanisms of Wnt Secretion and Signaling in Development. Mehta S, Hingole S, Chaudhary V. Front Cell Dev Biol 9 714746 (2021)
  28. WNT signalling events near the cell membrane and their pharmacological targeting for the treatment of cancer. Driehuis E, Clevers H. Br J Pharmacol 174 4547-4563 (2017)
  29. Wnt Signaling in Hematological Malignancies. Grainger S, Traver D, Willert K. Prog Mol Biol Transl Sci 153 321-341 (2018)
  30. Wingless Signaling: A Genetic Journey from Morphogenesis to Metastasis. Bejsovec A. Genetics 208 1311-1336 (2018)
  31. Wnt Signaling in Ewing Sarcoma, Osteosarcoma, and Malignant Peripheral Nerve Sheath Tumors. Pridgeon MG, Grohar PJ, Steensma MR, Williams BO. Curr Osteoporos Rep 15 239-246 (2017)
  32. Cortical bone development, maintenance and porosity: genetic alterations in humans and mice influencing chondrocytes, osteoclasts, osteoblasts and osteocytes. Isojima T, Sims NA. Cell Mol Life Sci 78 5755-5773 (2021)
  33. Plasticity of Paneth cells and their ability to regulate intestinal stem cells. Mei X, Gu M, Li M. Stem Cell Res Ther 11 349 (2020)
  34. An Intrinsic Oscillation of Gene Networks Inside Hair Follicle Stem Cells: An Additional Layer That Can Modulate Hair Stem Cell Activities. Daszczuk P, Mazurek P, Pieczonka TD, Olczak A, Boryń ŁM, Kobielak K. Front Cell Dev Biol 8 595178 (2020)
  35. Syndecan receptors: pericellular regulators in development and inflammatory disease. Gopal S, Arokiasamy S, Pataki C, Whiteford JR, Couchman JR. Open Biol 11 200377 (2021)
  36. Not All Wnt Activation Is Equal: Ligand-Dependent versus Ligand-Independent Wnt Activation in Colorectal Cancer. Kleeman SO, Leedham SJ. Cancers (Basel) 12 E3355 (2020)
  37. Genetic Approaches To Identifying Novel Osteoporosis Drug Targets. Brommage R. J Cell Biochem 116 2139-2145 (2015)
  38. The interplay between intrinsic and extrinsic Wnt signaling in controlling intestinal transformation. van Neerven SM, Vermeulen L. Differentiation 108 17-23 (2019)
  39. Proteome-wide analysis of protein lipidation using chemical probes: in-gel fluorescence visualization, identification and quantification of N-myristoylation, N- and S-acylation, O-cholesterylation, S-farnesylation and S-geranylgeranylation. Kallemeijn WW, Lanyon-Hogg T, Panyain N, Goya Grocin A, Ciepla P, Morales-Sanfrutos J, Tate EW. Nat Protoc 16 5083-5122 (2021)
  40. From top to bottom: Cell polarity in Hedgehog and Wnt trafficking. Gradilla AC, Sanchez-Hernandez D, Brunt L, Scholpp S. BMC Biol 16 37 (2018)
  41. Subversion of Niche-Signalling Pathways in Colorectal Cancer: What Makes and Breaks the Intestinal Stem Cell. Sphyris N, Hodder MC, Sansom OJ. Cancers (Basel) 13 1000 (2021)
  42. Activity-Based Sensing of S-Depalmitoylases: Chemical Technologies and Biological Discovery. Azizi SA, Kathayat RS, Dickinson BC. Acc Chem Res 52 3029-3038 (2019)
  43. Positional Information and Stem Cells Combine to Result in Planarian Regeneration. Reddien PW. Cold Spring Harb Perspect Biol 14 a040717 (2022)
  44. Vertebrate Axial Patterning: From Egg to Asymmetry. Houston DW. Adv Exp Med Biol 953 209-306 (2017)
  45. Advances of Wnt signalling pathway in dental development and potential clinical application. Lu X, Yang J, Zhao S, Liu S. Organogenesis 15 101-110 (2019)
  46. Wnt lipidation: Roles in trafficking, modulation, and function. Hosseini V, Dani C, Geranmayeh MH, Mohammadzadeh F, Nazari Soltan Ahmad S, Darabi M. J Cell Physiol 234 8040-8054 (2019)
  47. Signalling dynamics in embryonic development. Sonnen KF, Janda CY. Biochem J 478 4045-4070 (2021)
  48. The Role of WNT Pathway Mutations in Cancer Development and an Overview of Therapeutic Options. Groenewald W, Lund AH, Gay DM. Cells 12 990 (2023)
  49. Wnt Signaling in the Breast: From Development to Disease. Abreu de Oliveira WA, El Laithy Y, Bruna A, Annibali D, Lluis F. Front Cell Dev Biol 10 884467 (2022)
  50. Fatty acid recognition in the Frizzled receptor family. Nile AH, Hannoush RN. J Biol Chem 294 726-736 (2019)
  51. Ghrelin octanoylation by ghrelin O-acyltransferase: protein acylation impacting metabolic and neuroendocrine signalling. Davis TR, Pierce MR, Novak SX, Hougland JL. Open Biol 11 210080 (2021)
  52. Small-molecule inhibitors of carboxylesterase Notum. Zhao Y, Jolly S, Benvegnu S, Jones EY, Fish PV. Future Med Chem 13 1001-1015 (2021)
  53. New Twists in Drosophila Cell Signaling. Shilo BZ. J Biol Chem 291 7805-7808 (2016)
  54. Perspectives on Intra- and Intercellular Trafficking of Hedgehog for Tissue Patterning. Simon E, Aguirre-Tamaral A, Aguilar G, Guerrero I. J Dev Biol 4 E34 (2016)
  55. Systems-based approaches for investigation of inter-tissue communication. Seldin MM, Lusis AJ. J Lipid Res 60 450-455 (2019)
  56. Taking the Occam's Razor Approach to Hedgehog Lipidation and Its Role in Development. Manikowski D, Kastl P, Grobe K. J Dev Biol 6 E3 (2018)
  57. Canonical Wnt Signaling in the Pathology of Iron Overload-Induced Oxidative Stress and Age-Related Diseases. Armstrong A, Mandala A, Malhotra M, Gnana-Prakasam JP. Oxid Med Cell Longev 2022 7163326 (2022)
  58. Crosstalk between the Hippo Pathway and the Wnt Pathway in Huntington's Disease and Other Neurodegenerative Disorders. Sileo P, Simonin C, Melnyk P, Chartier-Harlin MC, Cotelle P. Cells 11 3631 (2022)
  59. Extracellular heparan sulfate proteoglycans and glycan-binding lectins orchestrate trans-synaptic signaling. Rushton E, Kopke DL, Broadie K. J Cell Sci 133 jcs244186 (2020)
  60. Protein Lipidation Types: Current Strategies for Enrichment and Characterization. Wang R, Chen YQ. Int J Mol Sci 23 2365 (2022)
  61. A Role for Frizzled and Their Post-Translational Modifications in the Mammalian Central Nervous System. Pascual-Vargas P, Salinas PC. Front Cell Dev Biol 9 692888 (2021)
  62. Global impact of proteoglycan science on human diseases. Xie C, Schaefer L, Iozzo RV. iScience 26 108095 (2023)
  63. Relationships of human α/β hydrolase fold proteins and other organophosphate-interacting proteins. Lenfant N, Bourne Y, Marchot P, Chatonnet A. Chem Biol Interact 259 343-351 (2016)
  64. Clone wars: From molecules to cell competition in intestinal stem cell homeostasis and disease. Colozza G, Park SY, Koo BK. Exp Mol Med 54 1367-1378 (2022)
  65. Regulation of Wnt distribution and function by Drosophila glypicans. Waghmare I, Page-McCaw A. J Cell Sci 135 jcs259405 (2022)
  66. Sfrp4 and the Biology of Cortical Bone. Chen R, Baron R, Gori F. Curr Osteoporos Rep 20 153-161 (2022)
  67. Signaling Network Centered on mTORC1 Dominates Mammalian Intestinal Stem Cell Ageing. Liang SJ, Zhou JY, Wang XQ. Stem Cell Rev Rep 17 842-849 (2021)
  68. The origin and evolution of Wnt signalling. Holzem M, Boutros M, Holstein TW. Nat Rev Genet 25 500-512 (2024)
  69. Ghrelin Acylation-A Post-Translational Tuning Mechanism Regulating Adult Hippocampal Neurogenesis. Sassi M, Morgan AH, Davies JS. Cells 11 765 (2022)
  70. The WNT/β-catenin system in chronic kidney disease-mineral bone disorder syndrome. Zhang L, Adu IK, Zhang H, Wang J. Int Urol Nephrol 55 2527-2538 (2023)
  71. Expression Levels of WNT Signaling Pathway Genes During Early Tooth Development. Song Y, Song F, Xiao X, Song Z, Liu S. Organogenesis 19 2212583 (2023)
  72. Hedgehog on the Move: Glypican-Regulated Transport and Gradient Formation in Drosophila. Jiménez-Jiménez C, Grobe K, Guerrero I. Cells 13 418 (2024)
  73. New insights in ubiquitin-dependent Wnt receptor regulation in tumorigenesis. Tsukiyama T. In Vitro Cell Dev Biol Anim 60 449-465 (2024)
  74. Shifting the Focus of Signaling Abnormalities in Colon Cancer. Brown MA, Ried T. Cancers (Basel) 14 784 (2022)
  75. The odontoblastic differentiation of dental mesenchymal stem cells: molecular regulation mechanism and related genetic syndromes. Pan H, Yang Y, Xu H, Jin A, Huang X, Gao X, Sun S, Liu Y, Liu J, Lu T, Wang X, Zhu Y, Jiang L. Front Cell Dev Biol 11 1174579 (2023)
  76. Advances in Regenerative Dentistry: A Systematic Review of Harnessing Wnt/β-Catenin in Dentin-Pulp Regeneration. Amir M, Jeevithan L, Barkat M, Fatima SH, Khan M, Israr S, Naseer F, Fayyaz S, Elango J, Wu W, Maté Sánchez de Val JE, Rahman SU. Cells 13 1153 (2024)
  77. Why Is Wnt/β-Catenin Not Yet Targeted in Routine Cancer Care? de Pellegars-Malhortie A, Picque Lasorsa L, Mazard T, Granier F, Prévostel C. Pharmaceuticals (Basel) 17 949 (2024)
  78. Wnt/β-catenin signaling pathway in carcinogenesis and cancer therapy. Song P, Gao Z, Bao Y, Chen L, Huang Y, Liu Y, Dong Q, Wei X. J Hematol Oncol 17 46 (2024)

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  1. Protein Lipidation: Occurrence, Mechanisms, Biological Functions, and Enabling Technologies. Jiang H, Zhang X, Chen X, Aramsangtienchai P, Tong Z, Lin H. Chem Rev 118 919-988 (2018)
  2. Identification of PSD-95 Depalmitoylating Enzymes. Yokoi N, Fukata Y, Sekiya A, Murakami T, Kobayashi K, Fukata M. J Neurosci 36 6431-6444 (2016)
  3. Molecular genetics and targeted therapy of WNT-related human diseases (Review). Katoh M, Katoh M. Int J Mol Med 40 587-606 (2017)
  4. Notum is required for neural and head induction via Wnt deacylation, oxidation, and inactivation. Zhang X, Cheong SM, Amado NG, Reis AH, MacDonald BT, Zebisch M, Jones EY, Abreu JG, He X. Dev Cell 32 719-730 (2015)
  5. Notum produced by Paneth cells attenuates regeneration of aged intestinal epithelium. Pentinmikko N, Iqbal S, Mana M, Andersson S, Cognetta AB, Suciu RM, Roper J, Luopajärvi K, Markelin E, Gopalakrishnan S, Smolander OP, Naranjo S, Saarinen T, Juuti A, Pietiläinen K, Auvinen P, Ristimäki A, Gupta N, Tammela T, Jacks T, Sabatini DM, Cravatt BF, Yilmaz ÖH, Katajisto P. Nature 571 398-402 (2019)
  6. Active and water-soluble form of lipidated Wnt protein is maintained by a serum glycoprotein afamin/α-albumin. Mihara E, Hirai H, Yamamoto H, Tamura-Kawakami K, Matano M, Kikuchi A, Sato T, Takagi J. Elife 5 e11621 (2016)
  7. NOTUM from Apc-mutant cells biases clonal competition to initiate cancer. Flanagan DJ, Pentinmikko N, Luopajärvi K, Willis NJ, Gilroy K, Raven AP, Mcgarry L, Englund JI, Webb AT, Scharaw S, Nasreddin N, Hodder MC, Ridgway RA, Minnee E, Sphyris N, Gilchrist E, Najumudeen AK, Romagnolo B, Perret C, Williams AC, Clevers H, Nummela P, Lähde M, Alitalo K, Hietakangas V, Hedley A, Clark W, Nixon C, Kirschner K, Jones EY, Ristimäki A, Leedham SJ, Fish PV, Vincent JP, Katajisto P, Sansom OJ. Nature 594 430-435 (2021)
  8. Apc-mutant cells act as supercompetitors in intestinal tumour initiation. van Neerven SM, de Groot NE, Nijman LE, Scicluna BP, van Driel MS, Lecca MC, Warmerdam DO, Kakkar V, Moreno LF, Vieira Braga FA, Sanches DR, Ramesh P, Ten Hoorn S, Aelvoet AS, van Boxel MF, Koens L, Krawczyk PM, Koster J, Dekker E, Medema JP, Winton DJ, Bijlsma MF, Morrissey E, Léveillé N, Vermeulen L. Nature 594 436-441 (2021)
  9. Structure and functional properties of Norrin mimic Wnt for signalling with Frizzled4, Lrp5/6, and proteoglycan. Chang TH, Hsieh FL, Zebisch M, Harlos K, Elegheert J, Jones EY. Elife 4 (2015)
  10. Endocardial Notch Signaling Promotes Cardiomyocyte Proliferation in the Regenerating Zebrafish Heart through Wnt Pathway Antagonism. Zhao L, Ben-Yair R, Burns CE, Burns CG. Cell Rep 26 546-554.e5 (2019)
  11. Fatty acylation of Wnt proteins. Nile AH, Hannoush RN. Nat Chem Biol 12 60-69 (2016)
  12. Orthogonal muscle fibres have different instructive roles in planarian regeneration. Scimone ML, Cote LE, Reddien PW. Nature 551 623-628 (2017)
  13. Lecture Fell-Muir Lecture: Heparan sulphate and the art of cell regulation: a polymer chain conducts the protein orchestra. Gallagher J. Int J Exp Pathol 96 203-231 (2015)
  14. A Strategy for Discovery of Endocrine Interactions with Application to Whole-Body Metabolism. Seldin MM, Koplev S, Rajbhandari P, Vergnes L, Rosenberg GM, Meng Y, Pan C, Phuong TMN, Gharakhanian R, Che N, Mäkinen S, Shih DM, Civelek M, Parks BW, Kim ED, Norheim F, Chella Krishnan K, Hasin-Brumshtein Y, Mehrabian M, Laakso M, Drevon CA, Koistinen HA, Tontonoz P, Reue K, Cantor RM, Björkegren JLM, Lusis AJ. Cell Metab 27 1138-1155.e6 (2018)
  15. Glypicans shield the Wnt lipid moiety to enable signalling at a distance. McGough IJ, Vecchia L, Bishop B, Malinauskas T, Beckett K, Joshi D, O'Reilly N, Siebold C, Jones EY, Vincent JP. Nature 585 85-90 (2020)
  16. Godzilla-dependent transcytosis promotes Wingless signalling in Drosophila wing imaginal discs. Yamazaki Y, Palmer L, Alexandre C, Kakugawa S, Beckett K, Gaugue I, Palmer RH, Vincent JP. Nat Cell Biol 18 451-457 (2016)
  17. Wnt/Notum spatial feedback inhibition controls neoblast differentiation to regulate reversible growth of the planarian brain. Hill EM, Petersen CP. Development 142 4217-4229 (2015)
  18. MetazSecKB: the human and animal secretome and subcellular proteome knowledgebase. Meinken J, Walker G, Cooper CR, Min XJ. Database (Oxford) 2015 bav077 (2015)
  19. Unsaturated fatty acyl recognition by Frizzled receptors mediates dimerization upon Wnt ligand binding. Nile AH, Mukund S, Stanger K, Wang W, Hannoush RN. Proc Natl Acad Sci U S A 114 4147-4152 (2017)
  20. A RECK-WNT7 Receptor-Ligand Interaction Enables Isoform-Specific Regulation of Wnt Bioavailability. Vallon M, Yuki K, Nguyen TD, Chang J, Yuan J, Siepe D, Miao Y, Essler M, Noda M, Garcia KC, Kuo CJ. Cell Rep 25 339-349.e9 (2018)
  21. Molecular Mechanism for Isoform-Selective Inhibition of Acyl Protein Thioesterases 1 and 2 (APT1 and APT2). Won SJ, Davda D, Labby KJ, Hwang SY, Pricer R, Majmudar JD, Armacost KA, Rodriguez LA, Rodriguez CL, Chong FS, Torossian KA, Palakurthi J, Hur ES, Meagher JL, Brooks CL, Stuckey JA, Martin BR. ACS Chem Biol 11 3374-3382 (2016)
  22. The SIAH E3 ubiquitin ligases promote Wnt/β-catenin signaling through mediating Wnt-induced Axin degradation. Ji L, Jiang B, Jiang X, Charlat O, Chen A, Mickanin C, Bauer A, Xu W, Yan X, Cong F. Genes Dev 31 904-915 (2017)
  23. Inferring regulatory networks from experimental morphological phenotypes: a computational method reverse-engineers planarian regeneration. Lobo D, Levin M. PLoS Comput Biol 11 e1004295 (2015)
  24. An evolutionarily-conserved Wnt3/β-catenin/Sp5 feedback loop restricts head organizer activity in Hydra. Vogg MC, Beccari L, Iglesias Ollé L, Rampon C, Vriz S, Perruchoud C, Wenger Y, Galliot B. Nat Commun 10 312 (2019)
  25. NOTUM inhibition increases endocortical bone formation and bone strength. Brommage R, Liu J, Vogel P, Mseeh F, Thompson AY, Potter DG, Shadoan MK, Hansen GM, Jeter-Jones S, Cui J, Bright D, Bardenhagen JP, Doree DD, Movérare-Skrtic S, Nilsson KH, Henning P, Lerner UH, Ohlsson C, Sands AT, Tarver JE, Powell DR, Zambrowicz B, Liu Q. Bone Res 7 2 (2019)
  26. Single-Cell Profiling and SCOPE-Seq Reveal Lineage Dynamics of Adult Ventricular-Subventricular Zone Neurogenesis and NOTUM as a Key Regulator. Mizrak D, Bayin NS, Yuan J, Liu Z, Suciu RM, Niphakis MJ, Ngo N, Lum KM, Cravatt BF, Joyner AL, Sims PA. Cell Rep 31 107805 (2020)
  27. Novel insights into Notum and glypicans regulation in colorectal cancer. De Robertis M, Arigoni M, Loiacono L, Riccardo F, Calogero RA, Feodorova Y, Tashkova D, Belovejdov V, Sarafian V, Cavallo F, Signori E. Oncotarget 6 41237-41257 (2015)
  28. Single Cell and Open Chromatin Analysis Reveals Molecular Origin of Epidermal Cells of the Skin. Fan X, Wang D, Burgmaier JE, Teng Y, Romano RA, Sinha S, Yi R. Dev Cell 47 21-37.e5 (2018)
  29. Wnt5a promotes Frizzled-4 signalosome assembly by stabilizing cysteine-rich domain dimerization. DeBruine ZJ, Ke J, Harikumar KG, Gu X, Borowsky P, Williams BO, Xu W, Miller LJ, Xu HE, Melcher K. Genes Dev 31 916-926 (2017)
  30. Identification of strong candidate genes for backfat and intramuscular fatty acid composition in three crosses based on the Iberian pig. Crespo-Piazuelo D, Criado-Mesas L, Revilla M, Castelló A, Noguera JL, Fernández AI, Ballester M, Folch JM. Sci Rep 10 13962 (2020)
  31. Immune infiltration profiling in gastric cancer and their clinical implications. Ren F, Zhao Q, Zhao M, Zhu S, Liu B, Bukhari I, Zhang K, Wu W, Fu Y, Yu Y, Tang Y, Zheng P, Mi Y. Cancer Sci 112 3569-3584 (2021)
  32. Runx2 Regulates Mouse Tooth Root Development Via Activation of WNT Inhibitor NOTUM. Wen Q, Jing J, Han X, Feng J, Yuan Y, Ma Y, Chen S, Ho TV, Chai Y. J Bone Miner Res 35 2252-2264 (2020)
  33. Application of a 3D Bioprinted Hepatocellular Carcinoma Cell Model in Antitumor Drug Research. Sun L, Yang H, Wang Y, Zhang X, Jin B, Xie F, Jin Y, Pang Y, Zhao H, Lu X, Sang X, Zhang H, Lin F, Sun W, Huang P, Mao Y. Front Oncol 10 878 (2020)
  34. A genome-wide view of the de-differentiation of central nervous system endothelial cells in culture. Sabbagh MF, Nathans J. Elife 9 e51276 (2020)
  35. Epithelial-mesenchymal transition transcription factors control pluripotent adult stem cell migration in vivo in planarians. Abnave P, Aboukhatwa E, Kosaka N, Thompson J, Hill MA, Aboobaker AA. Development 144 3440-3453 (2017)
  36. Fgf and Wnt signaling interaction in the mesenchymal niche regulates the murine hair cycle clock. Harshuk-Shabso S, Dressler H, Niehrs C, Aamar E, Enshell-Seijffers D. Nat Commun 11 5114 (2020)
  37. Mechanisms and inhibition of Porcupine-mediated Wnt acylation. Liu Y, Qi X, Donnelly L, Elghobashi-Meinhardt N, Long T, Zhou RW, Sun Y, Wang B, Li X. Nature 607 816-822 (2022)
  38. The WNT target SP5 negatively regulates WNT transcriptional programs in human pluripotent stem cells. Huggins IJ, Bos T, Gaylord O, Jessen C, Lonquich B, Puranen A, Richter J, Rossdam C, Brafman D, Gaasterland T, Willert K. Nat Commun 8 1034 (2017)
  39. Pentagone internalises glypicans to fine-tune multiple signalling pathways. Norman M, Vuilleumier R, Springhorn A, Gawlik J, Pyrowolakis G. Elife 5 e13301 (2016)
  40. Porcupine inhibitors impair trabecular and cortical bone mass and strength in mice. Funck-Brentano T, Nilsson KH, Brommage R, Henning P, Lerner UH, Koskela A, Tuukkanen J, Cohen-Solal M, Movérare-Skrtic S, Ohlsson C. J Endocrinol 238 13-23 (2018)
  41. Structural Basis of WLS/Evi-Mediated Wnt Transport and Secretion. Nygaard R, Yu J, Kim J, Ross DR, Parisi G, Clarke OB, Virshup DM, Mancia F. Cell 184 194-206.e14 (2021)
  42. Characterization of Tiki, a New Family of Wnt-specific Metalloproteases. Zhang X, MacDonald BT, Gao H, Shamashkin M, Coyle AJ, Martinez RV, He X. J Biol Chem 291 2435-2443 (2016)
  43. A single-cell atlas reveals unanticipated cell type complexity in Drosophila ovaries. Slaidina M, Gupta S, Banisch TU, Lehmann R. Genome Res 31 1938-1951 (2021)
  44. Mapping the molecular and structural specialization of the skin basement membrane for inter-tissue interactions. Tsutsui K, Machida H, Nakagawa A, Ahn K, Morita R, Sekiguchi K, Miner JH, Fujiwara H. Nat Commun 12 2577 (2021)
  45. Physiological controls of large-scale patterning in planarian regeneration: a molecular and computational perspective on growth and form. Durant F, Lobo D, Hammelman J, Levin M. Regeneration (Oxf) 3 78-102 (2016)
  46. Crystal structure of R-spondin 2 in complex with the ectodomains of its receptors LGR5 and ZNRF3. Zebisch M, Jones EY. J Struct Biol 191 149-155 (2015)
  47. LPS-Induced Inflammation Prior to Injury Exacerbates the Development of Post-Traumatic Osteoarthritis in Mice. Mendez ME, Sebastian A, Murugesh DK, Hum NR, McCool JL, Hsia AW, Christiansen BA, Loots GG. J Bone Miner Res 35 2229-2241 (2020)
  48. Roles of two types of heparan sulfate clusters in Wnt distribution and signaling in Xenopus. Mii Y, Yamamoto T, Takada R, Mizumoto S, Matsuyama M, Yamada S, Takada S, Taira M. Nat Commun 8 1973 (2017)
  49. Structure-based prediction of Wnt binding affinities for Frizzled-type cysteine-rich domains. Agostino M, Pohl SÖ, Dharmarajan A. J Biol Chem 292 11218-11229 (2017)
  50. The multifaceted role of GCM1 during trophoblast differentiation in the human placenta. Jeyarajah MJ, Jaju Bhattad G, Kelly RD, Baines KJ, Jaremek A, Yang FP, Okae H, Arima T, Dumeaux V, Renaud SJ. Proc Natl Acad Sci U S A 119 e2203071119 (2022)
  51. Cell signalling: Disarming Wnt. Nusse R. Nature 519 163-164 (2015)
  52. Essential long-range action of Wingless/Wnt in adult intestinal compartmentalization. Tian A, Duwadi D, Benchabane H, Ahmed Y. PLoS Genet 15 e1008111 (2019)
  53. Notum attenuates Wnt/β-catenin signaling to promote tracheal cartilage patterning. Gerhardt B, Leesman L, Burra K, Snowball J, Rosenzweig R, Guzman N, Ambalavanan M, Sinner D. Dev Biol 436 14-27 (2018)
  54. Stimulation of cortical bone formation with thienopyrimidine based inhibitors of Notum Pectinacetylesterase. Tarver JE, Pabba PK, Barbosa J, Han Q, Gardyan MW, Brommage R, Thompson AY, Schmidt JM, Wilson AGE, He W, Lombardo VK, Carson KG. Bioorg Med Chem Lett 26 1525-1528 (2016)
  55. Transcriptional Dynamics of Cultured Human Villous Cytotrophoblasts. Robinson JF, Kapidzic M, Gormley M, Ona K, Dent T, Seifikar H, Hamilton EG, Fisher SJ. Endocrinology 158 1581-1594 (2017)
  56. Widespread Rewiring of Genetic Networks upon Cancer Signaling Pathway Activation. Billmann M, Chaudhary V, ElMaghraby MF, Fischer B, Boutros M. Cell Syst 6 52-64.e4 (2018)
  57. Bridging the gap: heparan sulfate and Scube2 assemble Sonic hedgehog release complexes at the surface of producing cells. Jakobs P, Schulz P, Ortmann C, Schürmann S, Exner S, Rebollido-Rios R, Dreier R, Seidler DG, Grobe K. Sci Rep 6 26435 (2016)
  58. Cellular and Molecular Responses Unique to Major Injury Are Dispensable for Planarian Regeneration. Tewari AG, Stern SR, Oderberg IM, Reddien PW. Cell Rep 25 2577-2590.e3 (2018)
  59. Selective Irreversible Inhibitors of the Wnt-Deacylating Enzyme NOTUM Developed by Activity-Based Protein Profiling. Suciu RM, Cognetta AB, Potter ZE, Cravatt BF. ACS Med Chem Lett 9 563-568 (2018)
  60. Structure of the Dual-Mode Wnt Regulator Kremen1 and Insight into Ternary Complex Formation with LRP6 and Dickkopf. Zebisch M, Jackson VA, Zhao Y, Jones EY. Structure 24 1599-1605 (2016)
  61. Acoel regeneration mechanisms indicate an ancient role for muscle in regenerative patterning. Raz AA, Srivastava M, Salvamoser R, Reddien PW. Nat Commun 8 1260 (2017)
  62. Acylation-coupled lipophilic induction of polarisation (Acyl-cLIP): a universal assay for lipid transferase and hydrolase enzymes. Lanyon-Hogg T, Ritzefeld M, Sefer L, Bickel JK, Rudolf AF, Panyain N, Bineva-Todd G, Ocasio CA, O'Reilly N, Siebold C, Magee AI, Tate EW. Chem Sci 10 8995-9000 (2019)
  63. Arid1a is essential for intestinal stem cells through Sox9 regulation. Hiramatsu Y, Fukuda A, Ogawa S, Goto N, Ikuta K, Tsuda M, Matsumoto Y, Kimura Y, Yoshioka T, Takada Y, Maruno T, Hanyu Y, Tsuruyama T, Wang Z, Akiyama H, Takaishi S, Miyoshi H, Taketo MM, Chiba T, Seno H. Proc Natl Acad Sci U S A 116 1704-1713 (2019)
  64. Dentin Dysplasia in Notum Knockout Mice. Vogel P, Read RW, Hansen GM, Powell DR, Kantaputra PN, Zambrowicz B, Brommage R. Vet Pathol 53 853-862 (2016)
  65. NOTUM is a potential pharmacodynamic biomarker of Wnt pathway inhibition. Madan B, Ke Z, Lei ZD, Oliver FA, Oshima M, Lee MA, Rozen S, Virshup DM. Oncotarget 7 12386-12392 (2016)
  66. Neural control of body-plan axis in regenerating planaria. Pietak A, Bischof J, LaPalme J, Morokuma J, Levin M. PLoS Comput Biol 15 e1006904 (2019)
  67. Positional information specifies the site of organ regeneration and not tissue maintenance in planarians. Hill EM, Petersen CP. Elife 7 e33680 (2018)
  68. Transformed MDCK cells secrete elevated MMP1 that generates LAMA5 fragments promoting endothelial cell angiogenesis. Gopal SK, Greening DW, Zhu HJ, Simpson RJ, Mathias RA. Sci Rep 6 28321 (2016)
  69. In vitro reconstitution of Wnt acylation reveals structural determinants of substrate recognition by the acyltransferase human Porcupine. Lee CJ, Rana MS, Bae C, Li Y, Banerjee A. J Biol Chem 294 231-245 (2019)
  70. Hydra Mesoglea Proteome Identifies Thrombospondin as a Conserved Component Active in Head Organizer Restriction. Lommel M, Strompen J, Hellewell AL, Balasubramanian GP, Christofidou ED, Thomson AR, Boyle AL, Woolfson DN, Puglisi K, Hartl M, Holstein TW, Adams JC, Özbek S. Sci Rep 8 11753 (2018)
  71. Identification of specific posttranslational O-mycoloylations mediating protein targeting to the mycomembrane. Carel C, Marcoux J, Réat V, Parra J, Latgé G, Laval F, Demange P, Burlet-Schiltz O, Milon A, Daffé M, Tropis MG, Renault MAM. Proc Natl Acad Sci U S A 114 4231-4236 (2017)
  72. Osteoblast-derived NOTUM reduces cortical bone mass in mice and the NOTUM locus is associated with bone mineral density in humans. Movérare-Skrtic S, Nilsson KH, Henning P, Funck-Brentano T, Nethander M, Rivadeneira F, Coletto Nunes G, Koskela A, Tuukkanen J, Tuckermann J, Perret C, Souza PPC, Lerner UH, Ohlsson C. FASEB J 33 11163-11179 (2019)
  73. Progenitors oppositely polarize WNT activators and inhibitors to orchestrate tissue development. Matos I, Asare A, Levorse J, Ouspenskaia T, de la Cruz-Racelis J, Schuhmacher LN, Fuchs E. Elife 9 e54304 (2020)
  74. Discovery of 2-phenoxyacetamides as inhibitors of the Wnt-depalmitoleating enzyme NOTUM from an X-ray fragment screen. Atkinson BN, Steadman D, Zhao Y, Sipthorp J, Vecchia L, Ruza RR, Jeganathan F, Lines G, Frew S, Monaghan A, Kjær S, Bictash M, Jones EY, Fish PV. Medchemcomm 10 1361-1369 (2019)
  75. High variability of expression profiles of homeologous genes for Wnt, Hh, Notch, and Hippo signaling pathways in Xenopus laevis. Michiue T, Yamamoto T, Yasuoka Y, Goto T, Ikeda T, Nagura K, Nakayama T, Taira M, Kinoshita T. Dev Biol 426 270-290 (2017)
  76. Non-acylated Wnts Can Promote Signaling. Speer KF, Sommer A, Tajer B, Mullins MC, Klein PS, Lemmon MA. Cell Rep 26 875-883.e5 (2019)
  77. TRPM8 indicates poor prognosis in colorectal cancer patients and its pharmacological targeting reduces tumour growth in mice by inhibiting Wnt/β-catenin signalling. Pagano E, Romano B, Cicia D, Iannotti FA, Venneri T, Lucariello G, Nanì MF, Cattaneo F, De Cicco P, D'Armiento M, De Luca M, Lionetti R, Lama S, Stiuso P, Zoppoli P, Falco G, Marchianò S, Fiorucci S, Capasso R, Di Marzo V, Borrelli F, Izzo AA. Br J Pharmacol 180 235-251 (2023)
  78. Temperature and insulin signaling regulate body size in Hydra by the Wnt and TGF-beta pathways. Mortzfeld BM, Taubenheim J, Klimovich AV, Fraune S, Rosenstiel P, Bosch TCG. Nat Commun 10 3257 (2019)
  79. 4H-Thieno[3,2-c]chromene based inhibitors of Notum Pectinacetylesterase. Han Q, Pabba PK, Barbosa J, Mabon R, Healy JP, Gardyan MW, Terranova KM, Brommage R, Thompson AY, Schmidt JM, Wilson AG, Xu X, Tarver JE, Carson KG. Bioorg Med Chem Lett 26 1184-1187 (2016)
  80. Generation of Mice with Hepatocyte-Specific Conditional Deletion of Notum. Canal F, Charawi S, Grimber G, Houbron C, Drouet V, Colnot S, Terris B, Cavard C, Perret C. PLoS One 11 e0150997 (2016)
  81. Glypican 4 mediates Wnt transport between germ layers via signaling filopodia. Hu B, Rodriguez JJ, Kakkerla Balaraju A, Gao Y, Nguyen NT, Steen H, Suhaib S, Chen S, Lin F. J Cell Biol 220 e202009082 (2021)
  82. Notum coordinates synapse development via extracellular regulation of Wingless trans-synaptic signaling. Kopke DL, Lima SC, Alexandre C, Broadie K. Development 144 3499-3510 (2017)
  83. Phosphorothioate-Modified AP613-1 Specifically Targets GPC3 when Used for Hepatocellular Carcinoma Cell Imaging. Dong L, Zhou H, Zhao M, Gao X, Liu Y, Liu D, Guo W, Hu H, Xie Q, Fan J, Lin J, Wu W. Mol Ther Nucleic Acids 13 376-386 (2018)
  84. Proteolytic processing of palmitoylated Hedgehog peptides specifies the 3-4 intervein region of the Drosophila wing. Schürmann S, Steffes G, Manikowski D, Kastl P, Malkus U, Bandari S, Ohlig S, Ortmann C, Rebollido-Rios R, Otto M, Nüsse H, Hoffmann D, Klämbt C, Galic M, Klingauf J, Grobe K. Elife 7 e33033 (2018)
  85. Tissue-Specific Gain of RTK Signalling Uncovers Selective Cell Vulnerability during Embryogenesis. Fan Y, Richelme S, Avazeri E, Audebert S, Helmbacher F, Dono R, Maina F. PLoS Genet 11 e1005533 (2015)
  86. Wnts grasp the WIF domain of Wnt Inhibitory Factor 1 at two distinct binding sites. Kerekes K, Bányai L, Patthy L. FEBS Lett 589 3044-3051 (2015)
  87. activin-2 is required for regeneration of polarity on the planarian anterior-posterior axis. Cloutier JK, McMann CL, Oderberg IM, Reddien PW. PLoS Genet 17 e1009466 (2021)
  88. Single-cell transcriptomic profiling of the mouse cochlea: An atlas for targeted therapies. Jean P, Wong Jun Tai F, Singh-Estivalet A, Lelli A, Scandola C, Megharba S, Schmutz S, Roux S, Mechaussier S, Sudres M, Mouly E, Heritier AV, Bonnet C, Mallet A, Novault S, Libri V, Petit C, Michalski N. Proc Natl Acad Sci U S A 120 e2221744120 (2023)
  89. Stereoselective fatty acylation is essential for the release of lipidated WNT proteins from the acyltransferase Porcupine (PORCN). Tuladhar R, Yarravarapu N, Ma Y, Zhang C, Herbert J, Kim J, Chen C, Lum L. J Biol Chem 294 6273-6282 (2019)
  90. Carrier of Wingless (Cow) Regulation of Drosophila Neuromuscular Junction Development. Kopke DL, Leahy SN, Vita DJ, Lima SC, Newman ZL, Broadie K. eNeuro 7 ENEURO.0285-19.2020 (2020)
  91. Chemical Probes to Directly Profile Palmitoleoylation of Proteins. Zheng B, Jarugumilli GK, Chen B, Wu X. Chembiochem 17 2022-2027 (2016)
  92. Comparative Microarray Analysis of Proliferating and Differentiating Murine ENS Progenitor Cells. Neckel PH, Mohr R, Zhang Y, Hirt B, Just L. Stem Cells Int 2016 9695827 (2016)
  93. Scaffold-hopping identifies furano[2,3-d]pyrimidine amides as potent Notum inhibitors. Atkinson BN, Steadman D, Mahy W, Zhao Y, Sipthorp J, Bayle ED, Svensson F, Papageorgiou G, Jeganathan F, Frew S, Monaghan A, Bictash M, Jones EY, Fish PV. Bioorg Med Chem Lett 30 126751 (2020)
  94. Structure of the Wnt signaling enhancer LYPD6 and its interactions with the Wnt coreceptor LRP6. Zhao Y, Ren J, Lu W, Harlos K, Jones EY. FEBS Lett 592 3152-3162 (2018)
  95. The glycosphingolipid MacCer promotes synaptic bouton formation in Drosophila by interacting with Wnt. Huang Y, Huang S, Di Scala C, Wang Q, Wandall HH, Fantini J, Zhang YQ. Elife 7 e38183 (2018)
  96. Notum attenuates HBV-related liver fibrosis through inhibiting Wnt 5a mediated non-canonical pathways. Li W, Yu X, Zhu C, Wang Z, Zhao Z, Li Y, Zhang Y. Biol Res 52 10 (2019)
  97. Wingless mediated apoptosis: How cone cells direct the death of peripheral ommatidia in the developing Drosophila eye. Kumar SR, Patel H, Tomlinson A. Dev Biol 407 183-194 (2015)
  98. Design, synthesis, and biological evaluation of 2,4-dihydropyrano[2,3-c]pyrazole derivatives as autotaxin inhibitors. Pantsar T, Singha P, Nevalainen TJ, Koshevoy I, Leppänen J, Poso A, Niskanen JMA, Pasonen-Seppänen S, Savinainen JR, Laitinen T, Laitinen JT. Eur J Pharm Sci 107 97-111 (2017)
  99. Drosophila VAMP7 regulates Wingless intracellular trafficking. Gao H, He F, Lin X, Wu Y. PLoS One 12 e0186938 (2017)
  100. Genome-Wide Association Study and Post-genome-Wide Association Study Analysis for Spike Fertility and Yield Related Traits in Bread Wheat. Sheoran S, Jaiswal S, Raghav N, Sharma R, Sabhyata, Gaur A, Jaisri J, Tandon G, Singh S, Sharma P, Singh R, Iquebal MA, Angadi UB, Gupta A, Singh G, Singh GP, Rai A, Kumar D, Tiwari R. Front Plant Sci 12 820761 (2021)
  101. Novel Dental Anomaly-associated Mutations in WNT10A Protein Binding Sites. Kantaputra P, Jatooratthawichot P, Tantachamroon O, Nanekrungsan K, Intachai W, Olsen B, Tongsima S, Ngamphiw C, Cairns JRK. Int Dent J 73 79-86 (2023)
  102. Transcriptome Sequencing of the Striped Cucumber Beetle, Acalymma vittatum (F.), Reveals Numerous Sex-Specific Transcripts and Xenobiotic Detoxification Genes. Sparks ME, Nelson DR, Haber AI, Weber DC, Harrison RL. BioTech (Basel) 9 21 (2020)
  103. APC and P53 mutations synergise to create a therapeutic vulnerability to NOTUM inhibition in advanced colorectal cancer. Tian Y, Wang X, Cramer Z, Rhoades J, Estep KN, Ma X, Adams-Tzivelekidis S, Katona BW, Johnson FB, Yu Z, Blanco MA, Lengner CJ, Li N. Gut 72 2294-2306 (2023)
  104. An improved, scalable synthesis of Notum inhibitor LP-922056 using 1-chloro-1,2-benziodoxol-3-one as a superior electrophilic chlorinating agent. Willis NJ, Bayle ED, Papageorgiou G, Steadman D, Atkinson BN, Mahy W, Fish PV. Beilstein J Org Chem 15 2790-2797 (2019)
  105. Comparative transcriptome analysis reveals conserved branching morphogenesis related genes involved in chamber formation of catfish swimbladder. Yang Y, Fu Q, Liu Y, Wang X, Dunham R, Liu S, Bao L, Zeng Q, Zhou T, Li N, Qin Z, Jiang C, Gao D, Liu Z. Physiol Genomics 50 67-76 (2018)
  106. Design of a Potent, Selective, and Brain-Penetrant Inhibitor of Wnt-Deactivating Enzyme Notum by Optimization of a Crystallographic Fragment Hit. Willis NJ, Mahy W, Sipthorp J, Zhao Y, Woodward HL, Atkinson BN, Bayle ED, Svensson F, Frew S, Jeganathan F, Monaghan A, Benvegnù S, Jolly S, Vecchia L, Ruza RR, Kjær S, Howell S, Snijders AP, Bictash M, Salinas PC, Vincent JP, Jones EY, Whiting P, Fish PV. J Med Chem 65 7212-7230 (2022)
  107. Gene regulatory networks analysis of muscle-invasive bladder cancer subtypes using differential graphical model. Zhang Y, Chen Q, Gong M, Zeng Y, Gao D. BMC Genomics 22 863 (2021)
  108. Notum Deletion From Late-Stage Skeletal Cells Increases Cortical Bone Formation and Potentiates Skeletal Effects of Sclerostin Inhibition. Choi RB, Bullock WA, Hoggatt AM, Horan DJ, Pemberton EZ, Hong JM, Zhang X, He X, Robling AG. J Bone Miner Res 36 2413-2425 (2021)
  109. Prednisolone induces osteocytes apoptosis by promoting Notum expression and inhibiting PI3K/AKT/GSK3β/β-catenin pathway. Li C, Yang P, Liu B, Bu J, Liu H, Guo J, Hasegawa T, Si H, Li M. J Mol Histol 52 1081-1095 (2021)
  110. Reorganization of Metabolism during Cardiomyogenesis Implies Time-Specific Signaling Pathway Regulation. Barisón MJ, Pereira IT, Waloski Robert A, Dallagiovanna B. Int J Mol Sci 22 1330 (2021)
  111. Roads to the Fountain of Youth? Rejuvenating Intestinal Stem Cells. Larrick JW, Mendelsohn AR. Rejuvenation Res 22 342-347 (2019)
  112. Suppression of Wnt/β-Catenin Signaling Is Associated with Downregulation of Wnt1, PORCN, and Rspo2 in Alzheimer's Disease. Macyczko JR, Wang N, Zhao J, Ren Y, Lu W, Ikezu TC, Zhao N, Liu CC, Bu G, Li Y. Mol Neurobiol 60 26-35 (2023)
  113. Tiki proteins are glycosylphosphatidylinositol-anchored proteases. Li M, Zheng J, He X, Zhang X. FEBS Lett 596 1037-1046 (2022)
  114. Assessment of Wnt pathway selected gene expression levels in peripheral blood mononuclear cells (PBMCs) of postmenopausal patients with low bone mass. Stuss M, Migdalska-Sek M, Brzezianska-Lasota E, Michalska-Kasiczak M, Bazela P, Sewerynek E. Bosn J Basic Med Sci 21 461-470 (2021)
  115. Computational Analysis of the Inhibition Mechanism of NOTUM by the ONIOM Method. Yildiz I, Yildiz BS. ACS Omega 7 13333-13342 (2022)
  116. Pegasus, a small extracellular peptide enhancing short-range diffusion of Wingless. Magny EG, Platero AI, Bishop SA, Pueyo JI, Aguilar-Hidalgo D, Couso JP. Nat Commun 12 5660 (2021)
  117. Controlling Wnt Signaling Specificity and Implications for Targeting WNTs Pharmacologically. Sonavane PR, Willert K. Handb Exp Pharmacol 269 3-28 (2021)
  118. Enzymatic Cell-Surface Decoration with Proteins using Amphiphilic Lipid-Fused Peptide Substrates. Takahara M, Wakabayashi R, Fujimoto N, Minamihata K, Goto M, Kamiya N. Chemistry 25 7315-7321 (2019)
  119. Extracellular carriers control lipid-dependent secretion, delivery, and activity of WNT morphogens. de Almeida Magalhaes T, Liu J, Chan C, Borges KS, Zhang J, Kane AJ, Wierbowski BM, Ge Y, Liu Z, Mannam P, Zeve D, Weiss R, Breault DT, Huang P, Salic A. Dev Cell 59 244-261.e6 (2024)
  120. Heterotrimeric G proteins regulate planarian regeneration and behavior. Jenkins JE, Roberts-Galbraith RH. Genetics 223 iyad019 (2023)
  121. NOTUM promotes thermogenic capacity and protects against diet-induced obesity in male mice. Guo F, Seldin M, Péterfy M, Charugundla S, Zhou Z, Lee SD, Mouton A, Rajbhandari P, Zhang W, Pellegrini M, Tontonoz P, Lusis AJ, Shih DM. Sci Rep 11 16409 (2021)
  122. Preparation, characterization, and osteogenic activity mechanism of casein phosphopeptide-calcium chelate. Huang W, Lao L, Deng Y, Li Z, Liao W, Duan S, Xiao S, Cao Y, Miao J. Front Nutr 9 960228 (2022)
  123. Single-cell expression profile of Drosophila ovarian follicle stem cells illuminates spatial differentiation in the germarium. Dong Z, Pang L, Liu Z, Sheng Y, Li X, Thibault X, Reilein A, Kalderon D, Huang J. BMC Biol 21 143 (2023)
  124. Structural Analysis and Development of Notum Fragment Screening Hits. Zhao Y, Mahy W, Willis NJ, Woodward HL, Steadman D, Bayle ED, Atkinson BN, Sipthorp J, Vecchia L, Ruza RR, Harlos K, Jeganathan F, Constantinou S, Costa A, Kjær S, Bictash M, Salinas PC, Whiting P, Vincent JP, Fish PV, Jones EY. ACS Chem Neurosci 13 2060-2077 (2022)
  125. 5-Aza-2'-Deoxycytidine Ameliorates Choroidal Neovascularization by Inhibiting the Wnt/β-Catenin Signaling Pathway. Wu X, Yang X, Dai X, Chen X, Shen M, Dai J, Yuan F, Wang L, Yuan Y, Feng Y. Invest Ophthalmol Vis Sci 65 23 (2024)
  126. A single-cell atlas of the miracidium larva of Schistosoma mansoni reveals cell types, developmental pathways, and tissue architecture. Attenborough T, Rawlinson KA, Diaz Soria CL, Ambridge K, Sankaranarayanan G, Graham J, Cotton JA, Doyle SR, Rinaldi G, Berriman M. Elife 13 RP95628 (2024)
  127. Bioinformatics analysis of PAE family in Populus trichocarpa and responsiveness to carbon and nitrogen treatment. Xu C, Zhang S, Suo J, Chang R, Xu X, Xu Z, Yang C, Qu C, Liu G. 3 Biotech 11 370 (2021)
  128. Caffeine Limits Expansion of Apc-Deficient Clones in the Intestine by NOTUM Inhibition. van Driel MS, Linssen JDG, Flanagan DJ, Vlahov N, Nijman LE, de Groot NE, Elbers CC, Koster J, Sansom OJ, Vermeulen L, van Neerven SM. Cell Mol Gastroenterol Hepatol 16 652-655 (2023)
  129. Designed switch from covalent to non-covalent inhibitors of carboxylesterase Notum activity. Atkinson BN, Willis NJ, Zhao Y, Patel C, Frew S, Costelloe K, Magno L, Svensson F, Jones EY, Fish PV. Eur J Med Chem 251 115132 (2023)
  130. Development: Switching off WNT with precision. Baumann K. Nat Rev Mol Cell Biol 16 204 (2015)
  131. Exosome-Encapsulated miR-31, miR-192, and miR-375 Serve as Clinical Biomarkers of Gastric Cancer. He J, Wu J, Dong S, Xu J, Wang J, Zhou X, Rao Z, Gao W. J Oncol 2023 7335456 (2023)
  132. Exploratory study of sea buckthorn enhancing QiangGuYin efficacy by inhibiting CKIP-1 and Notum activating the Wnt/β-catenin signaling pathway and analysis of active ingredients by molecular docking. Yuan YF, Wang S, Zhou H, Tang BB, Liu Y, Huang H, He CJ, Chen TP, Fang MH, Liang BC, Mao YD, Qie FQ, Liu K, Shi XL. Front Pharmacol 13 994995 (2022)
  133. Frizzled receptors facilitate Tiki inhibition of Wnt signaling at the cell surface. Li M, Zheng J, Luo D, Xu K, Sheng R, MacDonald BT, He X, Zhang X. EMBO Rep 24 e55873 (2023)
  134. Heterogeneity in clone dynamics within and adjacent to intestinal tumours identified by Dre-mediated lineage tracing. Thorsen AS, Khamis D, Kemp R, Colombé M, Lourenço FC, Morrissey E, Winton D. Dis Model Mech 14 dmm046706 (2021)
  135. Inhibition of Mastermind-like 1 alleviates liver fibrosis induced by carbon tetrachloride in rats. Zheng S, Chen Y, Zheng S, He Z, Weng Z. Exp Biol Med (Maywood) 243 1099-1108 (2018)
  136. RNA expression of 6 genes from metastatic mucosal gastric cancer serves as the global prognostic marker for gastric cancer with functional validation. Suh YS, Lee J, George J, Seol D, Jeong K, Oh SY, Bang C, Jun Y, Kong SH, Lee HJ, Kim JI, Kim WH, Yang HK, Lee C. Br J Cancer 130 1571-1584 (2024)
  137. Step by step analysis on gene datasets of growth phases in hematopoietic stem cells. Elahimanesh M, Shokri N, Mohammadi P, Parvaz N, Najafi M. Biochem Biophys Rep 39 101737 (2024)
  138. Structure of WNT inhibitor adenomatosis polyposis coli down-regulated 1 (APCDD1), a cell-surface lipid-binding protein. Hsieh FL, Chang TH, Gabelli SB, Nathans J. Proc Natl Acad Sci U S A 120 e2217096120 (2023)
  139. The transcriptional regulatory network modulating human trophoblast stem cells to extravillous trophoblast differentiation. Kim M, Jang YJ, Lee M, Guo Q, Son AJ, Kakkad NA, Roland AB, Lee BK, Kim J. Nat Commun 15 1285 (2024)
  140. Wnt/Wingless signaling promotes lipid mobilization through signal-induced transcriptional repression. Liu M, Hemba-Waduge RU, Li X, Huang X, Liu TH, Han X, Wang Y, Ji JY. Proc Natl Acad Sci U S A 121 e2322066121 (2024)
  141. A spatiotemporal atlas of mouse liver homeostasis and regeneration. Xu J, Guo P, Hao S, Shangguan S, Shi Q, Volpe G, Huang K, Zuo J, An J, Yuan Y, Cheng M, Deng Q, Zhang X, Lai G, Nan H, Wu B, Shentu X, Wu L, Wei X, Jiang Y, Huang X, Pan F, Song Y, Li R, Wang Z, Liu C, Liu S, Li Y, Yang T, Xu Z, Du W, Li L, Ahmed T, You K, Dai Z, Li L, Qin B, Li Y, Lai L, Qin D, Chen J, Fan R, Li Y, Hou J, Ott M, Sharma AD, Cantz T, Schambach A, Kristiansen K, Hutchins AP, Göttgens B, Maxwell PH, Hui L, Xu X, Liu L, Chen A, Lai Y, Esteban MA. Nat Genet 56 953-969 (2024)
  142. Deciphering the cellular and molecular landscapes of Wnt/β-catenin signaling in mouse embryonic kidney development. Zhao H, Gong H, Zhu P, Sun C, Sun W, Zhou Y, Wu X, Qiu A, Wen X, Zhang J, Luo D, Liu Q, Li Y. Comput Struct Biotechnol J 23 3368-3378 (2024)
  143. Dysregulation of Glypicans and Notum in Osteoarthritis: Plasma Levels, Bone Marrow Mesenchymal Stromal Cells and Osteoblasts. González-Guede I, López-Ramos M, Rodríguez-Rodríguez L, Abasolo L, Mucientes A, Fernández-Gutiérrez B. Cells 13 852 (2024)
  144. Elucidate growth control mechanisms using reconstructed spatiotemporal distributions of signaling events. Zhu H. Comput Struct Biotechnol J 19 3618-3627 (2021)
  145. Identification and Characterization of ATOH7-Regulated Target Genes and Pathways in Human Neuroretinal Development. Atac D, Maggi K, Feil S, Maggi J, Cuevas E, Sowden JC, Koller S, Berger W. Cells 13 1142 (2024)
  146. Large-scale synthesis of Notum inhibitor 1-(2,4-dichloro-3-(trifluoromethyl)-phenyl)-1H-1,2,3-triazole (ARUK3001185) employing a modified Sakai reaction as the key step. Atkinson BN, Willis NJ, Smith J, Gill R, Ali J, Xu Z, Lai PS, Fish PV. RSC Adv 12 26497-26503 (2022)
  147. Notum regulates the cusp and root patterns in mouse molar. Adasooriya D, Jeong JK, Kyeong M, Kan S, Kim J, Cho ES, Cho SW. Sci Rep 14 13633 (2024)
  148. On-demand chlorine dioxide solution enhances odontoblast differentiation through desulfation of cell surface heparan sulfate proteoglycan and subsequent activation of canonical Wnt signaling. Inubushi T, Priyanka N, Watanabe M, Takahashi Y, Kusano S, Kurosaka H, Papagerakis S, Papagerakis P, Hayashi M, Yamashiro T. Front Cell Dev Biol 11 1271455 (2023)
  149. Pleiotropic role of NOTUM in colorectal cancer. van Driel MS, Linssen JDG, van Neerven SM, Vermeulen L. Gut 72 2222-2223 (2023)
  150. Regulation of Cell Polarity by Posttranslational Protein Palmitoylation. Chen B, Guarino C, Azzi A, Erb H, Wu X. Methods Mol Biol 2438 107-121 (2022)


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