cd07935

N-terminal sub-domain of the Rel homology domain (RHD) of nuclear factor of kappa B1 (NF-kappa B1)

CDD entry
Member databaseCDD
CDD typedomain
Short nameRHD-n_NFkB1
SetRHD-n

Description

Proteins containing the Rel homology domain (RHD) are metazoan transcription factors. The RHD is composed of two structural sub-domains; this model characterizes the N-terminal RHD sub-domain of the NF-kappa B1 family of transcription factors, a class I member of the NF-kappa B family. In class I NF-kappa Bs, the RHD domain co-occurs with C-terminal ankyrin repeats. NF-kappa B1 is commonly referred to as p105 or p50 (proteolytically processed form). NF-kappa B proteins are part of a protein complex that acts as a transcription factor, which is responsible for regulating a host of cellular responses to a variety of stimuli. This complex tightly regulates the expression of a large number of genes, and is involved in processes such as adaptive and innate immunity, stress response, inflammation, cell adhesion, proliferation and apoptosis. The cytosolic NF-kappa B complex is activated via phosphorylation of the ankyrin-repeat containing inhibitory protein I-kappa B, which dissociates from the complex and exposes the nuclear localization signal of the heterodimer (NF-kappa B and REL). NF-kappa B1 is involved in the canonical NF-kappa B signaling pathway which is activated by many agonists and is essential in immune and inflammatory responses, as well as cell survival. p105 is involved in its own specific NF-kappa B signaling pathway which is also implicated in immune and inflammatory responses. p105 may also act as an I-kappa B due to its C-terminal ankyrin repeats. It is also involved in mitogen-activated protein kinase (MAPK) signaling as its degradation leads to the activation of TPL-2, a MAPK kinase kinase which activates ERK pathways.
[25, 21, 16, 17, 24, 40, 8, 23, 11, 35, 14, 36, 5, 4, 27, 20, 34, 30, 42, 22, 10, 3, 31, 29, 7, 15, 2, 37, 1, 9, 19, 39, 6, 33, 43, 38, 13, 28, 32, 12, 41, 26, 18]

References

1.Dual roles of NF-kappaB in cell survival and implications of NF-kappaB inhibitors in neuroprotective therapy. Qin ZH, Tao LY, Chen X. Acta Pharmacol Sin 28, 1859-72, (2007). PMID: 18031598

2.Nuclear factor-kappaB activation: from bench to bedside. Sethi G, Sung B, Aggarwal BB. Exp Biol Med (Maywood) 233, 21-31, (2008). PMID: 18156302

3.Focus on molecules: nuclear factor-kappaB. Srivastava SK, Ramana KV. Exp Eye Res 88, 2-3, (2009). PMID: 18472097

4.Proteasome-mediated degradation of IkappaBalpha and processing of p105 in Crohn disease and ulcerative colitis. Visekruna A, Joeris T, Seidel D, Kroesen A, Loddenkemper C, Zeitz M, Kaufmann SH, Schmidt-Ullrich R, Steinhoff U. J Clin Invest 116, 3195-203, (2006). PMID: 17124531

5.Peripheral blood mononuclear cell NF-kappaB p105 mRNA decreases during asthmatic attacks. Matsumura Y. Biomed Pharmacother 62, 147-52, (2008). PMID: 17913447

6.Role of nuclear factor kappaB in the central nervous system. Malek R, Borowicz KK, Jargiello M, Czuczwar SJ. Pharmacol Rep 59, 25-33, (2007). PMID: 17377203

7.NF-kappa B: a new player in angiostatic therapy. Tabruyn SP, Griffioen AW. Angiogenesis 11, 101-6, (2008). PMID: 18283548

8.Structure of the NF-kappa B p50 homodimer bound to DNA. Muller CW, Rey FA, Sodeoka M, Verdine GL, Harrison SC. Nature 373, 311-7, (1995). View articlePMID: 7830764

9.NF-kappa B-mediated adaptive resistance to ionizing radiation. Ahmed KM, Li JJ. Free Radic Biol Med 44, 1-13, (2008). PMID: 17967430

10.Crosstalk via the NF-kappaB signaling system. Basak S, Hoffmann A. Cytokine Growth Factor Rev 19, 187-97, (2008). PMID: 18515173

11.Proteolysis of NF-kappaB1 p105 is essential for T cell antigen receptor-induced proliferation. Sriskantharajah S, Belich MP, Papoutsopoulou S, Janzen J, Tybulewicz V, Seddon B, Ley SC. Nat Immunol 10, 38-47, (2009). PMID: 19060899

12.NF-kappa B, KBF1, dorsal, and related matters. Gilmore TD. Cell 62, 841-3, (1990). View articlePMID: 2203533

13.NF-kappaB and the regulation of hematopoiesis. Bottero V, Withoff S, Verma IM. Cell Death Differ 13, 785-97, (2006). PMID: 16528384

14.Linkage of Crohn's disease-related serological phenotypes: NFKB1 haplotypes are associated with anti-CBir1 and ASCA, and show reduced NF-kappaB activation. Takedatsu H, Taylor KD, Mei L, McGovern DP, Landers CJ, Gonsky R, Cong Y, Vasiliauskas EA, Ippoliti A, Elson CO, Rotter JI, Targan SR. Gut 58, 60-7, (2009). PMID: 18832525

15.NF-kappaB signaling in skeletal muscle: prospects for intervention in muscle diseases. Mourkioti F, Rosenthal N. J Mol Med (Berl) 86, 747-59, (2008). PMID: 18246321

16.Regulation and function of NF-kappaB transcription factors in the immune system. Vallabhapurapu S, Karin M. Annu. Rev. Immunol. 27, 693-733, (2009). View articlePMID: 19302050

17.NF-kappa B1 p105 regulates T cell homeostasis and prevents chronic inflammation. Chang M, Lee AJ, Fitzpatrick L, Zhang M, Sun SC. J Immunol 182, 3131-8, (2009). PMID: 19234210

18.Signaling to NF-kappaB. Hayden MS, Ghosh S. Genes Dev. 18, 2195-224, (2004). View articlePMID: 15371334

19.NF-kappaB as a potential molecular target for cancer therapy. Lee CH, Jeon YT, Kim SH, Song YS. Biofactors 29, 19-35, (2007). PMID: 17611291

20.Multiple redox regulation in NF-kappaB transcription factor activation. Piette J, Piret B, Bonizzi G, Schoonbroodt S, Merville MP, Legrand-Poels S, Bours V. Biol. Chem. 378, 1237-45, (1997). PMID: 9426183

21.Functions of NF-kappaB1 and NF-kappaB2 in immune cell biology. Beinke S, Ley SC. Biochem J 382, 393-409, (2004). PMID: 15214841

22.The inducible transcription factor NF-kappa B: structure-function relationship of its protein subunits. Grimm S, Baeuerle PA. Biochem J 290 ( Pt 2), 297-308, (1993). PMID: 8452515

23.Platelet-activating factor induces the processing of nuclear factor-kappaB p105 into p50, which mediates acute bowel injury in mice. Liu SX, Tian R, Baskind H, Hsueh W, De Plaen IG. Am J Physiol Gastrointest Liver Physiol 297, G76-81, (2009). PMID: 19460845

24.Synergism between NF-kappa B1/p50 and Notch2 during the development of marginal zone B lymphocytes. Moran ST, Cariappa A, Liu H, Muir B, Sgroi D, Boboila C, Pillai S. J Immunol 179, 195-200, (2007). PMID: 17579038

25.Nuclear factor-kappaB1: regulation and function. Pereira SG, Oakley F. Int J Biochem Cell Biol 40, 1425-30, (2008). PMID: 17693123

26.Shared principles in NF-kappaB signaling. Hayden MS, Ghosh S. Cell 132, 344-62, (2008). PMID: 18267068

27.The rel family of proteins. Rushlow C, Warrior R. Bioessays 14, 89-95, (1992). PMID: 1533515

28.NF-kappaB links innate immunity to the hypoxic response through transcriptional regulation of HIF-1alpha. Rius J, Guma M, Schachtrup C, Akassoglou K, Zinkernagel AS, Nizet V, Johnson RS, Haddad GG, Karin M. Nature 453, 807-11, (2008). PMID: 18432192

29.Estrogen, NFkappaB, and the heat shock response. Stice JP, Knowlton AA. Mol Med 14, 517-27, (2008). PMID: 18431462

30.Rel/NF-kappa B transcription factors and I kappa B inhibitors: evolution from a unique common ancestor. Huguet C, Crepieux P, Laudet V. Oncogene 15, 2965-74, (1997). PMID: 9416840

31.NF-kappaB and cancer-identifying targets and mechanisms. Naugler WE, Karin M. Curr Opin Genet Dev 18, 19-26, (2008). PMID: 18440219

32.NF-kappa B: a pleiotropic mediator of inducible and tissue-specific gene control. Lenardo MJ, Baltimore D. Cell 58, 227-9, (1989). PMID: 2665943

33.Nuclear factor-kappaB in development, prevention, and therapy of cancer. Van Waes C. Clin Cancer Res 13, 1076-82, (2007). PMID: 17317814

34.The inhibitory ankyrin and activator Rel proteins. Nolan GP, Baltimore D. Curr Opin Genet Dev 2, 211-20, (1992). PMID: 1386268

35.The prognostic impact of NF-kappaB p105, vimentin, E-cadherin and Par6 expression in epithelial and stromal compartment in non-small-cell lung cancer. Al-Saad S, Al-Shibli K, Donnem T, Persson M, Bremnes RM, Busund LT. Br J Cancer 99, 1476-83, (2008). PMID: 18854838

36.Prostaglandin E receptor type 4-associated protein interacts directly with NF-kappaB1 and attenuates macrophage activation. Minami M, Shimizu K, Okamoto Y, Folco E, Ilasaca ML, Feinberg MW, Aikawa M, Libby P. J Biol Chem 283, 9692-703, (2008). PMID: 18270204

37.Nuclear factor-kappaB, an unappreciated tumor suppressor. Chen F, Castranova V. Cancer Res 67, 11093-8, (2007). PMID: 18056430

38.The nuclear factor-kappaB (NF-kappaB): from a versatile transcription factor to a ubiquitous therapeutic target. Yates LL, Gorecki DC. Acta Biochim Pol 53, 651-62, (2006). PMID: 17068636

39.Beyond IkappaBs: alternative regulation of NF-kappaB activity. Neumann M, Naumann M. FASEB J. 21, 2642-54, (2007). PMID: 17431096

40.Sensitivity of TLR4- and -7-induced NF kappa B1 p105-TPL2-ERK pathway to TNF-receptor-associated-factor-6 revealed by RNAi in mouse macrophages. Loniewski KJ, Patial S, Parameswaran N. Mol. Immunol. 44, 3715-23, (2007). View articlePMID: 17507094

41.NF-kappa B: a lesson in family values. Thanos D, Maniatis T. Cell 80, 529-32, (1995). PMID: 7867060

42.The transcription factor NF-kappaB in the demosponge Amphimedon queenslandica: insights on the evolutionary origin of the Rel homology domain. Gauthier M, Degnan BM. Dev. Genes Evol. 218, 23-32, (2008). PMID: 18175145

43.Nuclear factor-kappaB: activation and regulation during toll-like receptor signaling. Carmody RJ, Chen YH. Cell Mol Immunol 4, 31-41, (2007). PMID: 17349209

Integrated to
External Links
This website requires cookies, and the limited processing of your personal data in order to function. By using the site you are agreeing to this as outlined in our Privacy Notice and Terms of Use.