6g86 › Citations

A PxL motif promotes timely cell cycle substrate dephosphorylation by the Cdc14 phosphatase.

<div class='caption-title'>Identification of the PxL Cdc14 docking motif.</div>
<div class='caption-title'>The PxL motif promotes Cbk1 dephosphorylation.</div>
<div class='caption-title'>The PxL motif inserts into deep surface pockets on the dimeric Cdc14 phosphatase.</div>
Kataria M, Mouilleron S, Seo MH, Corbi-Verge C, Kim PM, Uhlmann F
OpenAccess logo Nat Struct Mol Biol 25 1093-1102 (2018)
Related entries: 6g84, 6g85

Cited: 21 times
EuropePMC logo PMID: 30455435

Abstract

The cell division cycle consists of a series of temporally ordered events. Cell cycle kinases and phosphatases provide key regulatory input, but how the correct substrate phosphorylation and dephosphorylation timing is achieved is incompletely understood. Here we identify a PxL substrate recognition motif that instructs dephosphorylation by the budding yeast Cdc14 phosphatase during mitotic exit. The PxL motif was prevalent in Cdc14-binding peptides enriched in a phage display screen of native disordered protein regions. PxL motif removal from the Cdc14 substrate Cbk1 delays its dephosphorylation, whereas addition of the motif advances dephosphorylation of otherwise late Cdc14 substrates. Crystal structures of Cdc14 bound to three PxL motif substrate peptides provide a molecular explanation for PxL motif recognition on the phosphatase surface. Our results illustrate the sophistication of phosphatase-substrate interactions and identify them as an important determinant of ordered cell cycle progression.

Articles - 6g86 mentioned but not cited (2)

  1. The Eukaryotic Linear Motif resource: 2022 release. Kumar M, Michael S, Alvarado-Valverde J, Mészáros B, Sámano-Sánchez H, Zeke A, Dobson L, Lazar T, Örd M, Nagpal A, Farahi N, Käser M, Kraleti R, Davey NE, Pancsa R, Chemes LB, Gibson TJ. Nucleic Acids Res 50 D497-D508 (2022)
  2. A PxL motif promotes timely cell cycle substrate dephosphorylation by the Cdc14 phosphatase. Kataria M, Mouilleron S, Seo MH, Corbi-Verge C, Kim PM, Uhlmann F. Nat Struct Mol Biol 25 1093-1102 (2018)


Reviews citing this publication (4)

  1. Promoter DNA hypermethylation - Implications for Alzheimer's disease. Liu Y, Wang M, Marcora EM, Zhang B, Goate AM. Neurosci Lett 711 134403 (2019)
  2. The Multiple Roles of the Cdc14 Phosphatase in Cell Cycle Control. Manzano-López J, Monje-Casas F. Int J Mol Sci 21 E709 (2020)
  3. Interplay between Phosphatases and the Anaphase-Promoting Complex/Cyclosome in Mitosis. Kataria M, Yamano H. Cells 8 E814 (2019)
  4. Orchestrating serine/threonine phosphorylation and elucidating downstream effects by short linear motifs. Kliche J, Ivarsson Y. Biochem J 479 1-22 (2022)

Articles citing this publication (15)

  1. Cyclin-Specific Docking Mechanisms Reveal the Complexity of M-CDK Function in the Cell Cycle. Örd M, Venta R, Möll K, Valk E, Loog M. Mol Cell 75 76-89.e3 (2019)
  2. Systematic Discovery of Short Linear Motifs Decodes Calcineurin Phosphatase Signaling. Wigington CP, Roy J, Damle NP, Yadav VK, Blikstad C, Resch E, Wong CJ, Mackay DR, Wang JT, Krystkowiak I, Bradburn DA, Tsekitsidou E, Hong SH, Kaderali MA, Xu SL, Stearns T, Gingras AC, Ullman KS, Ivarsson Y, Davey NE, Cyert MS. Mol Cell 79 342-358.e12 (2020)
  3. Cdc14 and PP2A Phosphatases Cooperate to Shape Phosphoproteome Dynamics during Mitotic Exit. Touati SA, Hofbauer L, Jones AW, Snijders AP, Kelly G, Uhlmann F. Cell Rep 29 2105-2119.e4 (2019)
  4. A new linear cyclin docking motif that mediates exclusively S-phase CDK-specific signaling. Faustova I, Bulatovic L, Matiyevskaya F, Valk E, Örd M, Loog M. EMBO J 40 e105839 (2021)
  5. Comprehensive Analysis of G1 Cyclin Docking Motif Sequences that Control CDK Regulatory Potency In Vivo. Bandyopadhyay S, Bhaduri S, Örd M, Davey NE, Loog M, Pryciak PM. Curr Biol 30 4454-4466.e5 (2020)
  6. Multiple Layers of Phospho-Regulation Coordinate Metabolism and the Cell Cycle in Budding Yeast. Zhang L, Winkler S, Schlottmann FP, Kohlbacher O, Elias JE, Skotheim JM, Ewald JC. Front Cell Dev Biol 7 338 (2019)
  7. Proline-Rich Motifs Control G2-CDK Target Phosphorylation and Priming an Anchoring Protein for Polo Kinase Localization. Örd M, Puss KK, Kivi R, Möll K, Ojala T, Borovko I, Faustova I, Venta R, Valk E, Kõivomägi M, Loog M. Cell Rep 31 107757 (2020)
  8. Screening Intrinsically Disordered Regions for Short Linear Binding Motifs. Ali M, Simonetti L, Ivarsson Y. Methods Mol Biol 2141 529-552 (2020)
  9. Proteome-wide screening for mitogen-activated protein kinase docking motifs and interactors. Shi G, Song C, Torres Robles J, Salichos L, Lou HJ, Lam TT, Gerstein M, Turk BE. Sci Signal 16 eabm5518 (2023)
  10. Cdc14 spatiotemporally dephosphorylates Atg13 to activate autophagy during meiotic divisions. Feng W, Argüello-Miranda O, Qian S, Wang F. J Cell Biol 221 e202107151 (2022)
  11. Cdc6 is sequentially regulated by PP2A-Cdc55, Cdc14, and Sic1 for origin licensing in S. cerevisiae. Philip J, Örd M, Silva A, Singh S, Diffley JF, Remus D, Loog M, Ikui AE. Elife 11 e74437 (2022)
  12. Conservation of Cdc14 phosphatase specificity in plant fungal pathogens: implications for antifungal development. DeMarco AG, Milholland KL, Pendleton AL, Whitney JJ, Zhu P, Wesenberg DT, Nambiar M, Pepe A, Paula S, Chmielewski J, Wisecaver JH, Tao WA, Hall MC. Sci Rep 10 12073 (2020)
  13. Cdc14 phosphatase contributes to cell wall integrity and pathogenesis in Candida albicans. Milholland KL, AbdelKhalek A, Baker KM, Hoda S, DeMarco AG, Naughton NH, Koeberlein AN, Lorenz GR, Anandasothy K, Esperilla-Muñoz A, Narayanan SK, Correa-Bordes J, Briggs SD, Hall MC. Front Microbiol 14 1129155 (2023)
  14. Docking to a Basic Helix Promotes Specific Phosphorylation by G1-Cdk1. Faustova I, Möll K, Valk E, Loog M, Örd M. Int J Mol Sci 22 9514 (2021)
  15. Regulation of Rim4 distribution, function, and stability during meiosis by PKA, Cdc14, and 14-3-3 proteins. Zhang R, Feng W, Qian S, Li S, Wang F. Cell Rep 42 113052 (2023)


Quick links