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Nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)

PDB rendering based on 1bfs.
Available structures
1bfs, 1ikn, 1le5, 1le9, 1lei, 1nfi, 1nfk, 1ooa, 1svc, 1u36, 1u3j, 1u3y, 1u3z, 1u41, 1u42, 1vkx, 2dbf, 2i9t
Identifiers
Symbols NFKB1; DKFZp686C01211; EBP-1; KBF1; MGC54151; NF-kappa-B; NFKB-p105; NFKB-p50
External IDs OMIM164011 MGI97312 HomoloGene2971 GeneCards: NFKB1 Gene
RNA expression pattern
PBB GE NFKB1 209239 at.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 4790 18033
Ensembl ENSG00000109320 ENSMUSG00000028163
UniProt P19838 P25799
RefSeq (mRNA) NM_003998 NM_008689
RefSeq (protein) NP_003989 NP_032715
Location (UCSC) Chr 4:
103.64 - 103.76 Mb
Chr 3:
135.29 - 135.61 Mb
PubMed search [1] [2]

Nuclear factor NF-kappa-B p105 subunit is a protein that in humans is encoded by the NFKB1 gene.[1]

This gene encodes a 105 kD protein which can undergo cotranslational processing by the 26S proteasome to produce a 50 kD protein. The 105 kD protein is a Rel protein-specific transcription inhibitor and the 50 kD protein is a DNA binding subunit of the NF-kappaB (NF-κB) protein complex. NF-κB is a transcription factor that is activated by various intra- and extra-cellular stimuli such as cytokines, oxidant-free radicals, ultraviolet irradiation, and bacterial or viral products. Activated NF-κB translocates into the nucleus and stimulates the expression of genes involved in a wide variety of biological functions; over 200 known genes are targets of NF-κB in various cell types, under specific conditions. Inappropriate activation of NF-κB has been associated with a number of inflammatory diseases while persistent inhibition of NF-κB leads to inappropriate immune cell development or delayed cell growth.[2]

Contents

Interactions

NFKB1 has been shown to interact with NFKBIE,[3] IKK2,[4][5] MAP3K7IP2,[6] STAT6,[7] ITGB3BP,[8] IκBα,[9][10] NFKB2,[11] RELA,[11][12] RELB,[11] TSC22D3,[13] NOTCH1,[14][15] HDAC1,[16] LYL1,[17] BCL3,[18][19][5] STAT3,[20] MAP3K8,[21][11] MEN1,[22] Nuclear receptor coactivator 1[23][24] and HMGA2.[25]

References

  1. ^ Meyer R, Hatada EN, Hohmann HP, Haiker M, Bartsch C, Rothlisberger U, Lahm HW, Schlaeger EJ, van Loon AP, Scheidereit C (Mar 1991). "Cloning of the DNA-binding subunit of human nuclear factor kappa B: the level of its mRNA is strongly regulated by phorbol ester or tumor necrosis factor alpha". Proc Natl Acad Sci U S A 88 (3): 966–70. PMID 1992489.  
  2. ^ "Entrez Gene: NF-κB nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4790.  
  3. ^ Li, Z; Nabel G J (Oct. 1997). "A new member of the I kappaB protein family, I kappaB epsilon, inhibits RelA (p65)-mediated NF-kappaB transcription". Mol. Cell. Biol. (UNITED STATES) 17 (10): 6184–90. ISSN 0270-7306. PMID 9315679.  
  4. ^ Heissmeyer, V; Krappmann D, Hatada E N, Scheidereit C (Feb. 2001). "Shared pathways of IkappaB kinase-induced SCF(betaTrCP)-mediated ubiquitination and degradation for the NF-kappaB precursor p105 and IkappaBalpha". Mol. Cell. Biol. (United States) 21 (4): 1024–35. doi:10.1128/MCB.21.4.1024-1035.2001. ISSN 0270-7306. PMID 11158290.  
  5. ^ a b Heissmeyer, V; Krappmann D, Wulczyn F G, Scheidereit C (Sep. 1999). "NF-kappaB p105 is a target of IkappaB kinases and controls signal induction of Bcl-3-p50 complexes". EMBO J. (ENGLAND) 18 (17): 4766–78. doi:10.1093/emboj/18.17.4766. ISSN 0261-4189. PMID 10469655.  
  6. ^ Baek, Sung Hee; Ohgi Kenneth A, Rose David W, Koo Edward H, Glass Christopher K, Rosenfeld Michael G (Jul. 2002). "Exchange of N-CoR corepressor and Tip60 coactivator complexes links gene expression by NF-kappaB and beta-amyloid precursor protein". Cell (United States) 110 (1): 55–67. ISSN 0092-8674. PMID 12150997.  
  7. ^ Shen, C H; Stavnezer J (Jun. 1998). "Interaction of stat6 and NF-kappaB: direct association and synergistic activation of interleukin-4-induced transcription". Mol. Cell. Biol. (UNITED STATES) 18 (6): 3395–404. ISSN 0270-7306. PMID 9584180.  
  8. ^ Besta, Felicitas; Massberg Steffen, Brand Korbinian, Müller Elke, Page Sharon, Grüner Sabine, Lorenz Michael, Sadoul Karin, Kolanus Waldemar, Lengyel Ernst, Gawaz Meinrad (Oct. 2002). "Role of beta(3)-endonexin in the regulation of NF-kappaB-dependent expression of urokinase-type plasminogen activator receptor". J. Cell. Sci. (England) 115 (Pt 20): 3879–88. ISSN 0021-9533. PMID 12244126.  
  9. ^ Hay, D C; Kemp G D, Dargemont C, Hay R T (May. 2001). "Interaction between hnRNPA1 and IkappaBalpha is required for maximal activation of NF-kappaB-dependent transcription". Mol. Cell. Biol. (United States) 21 (10): 3482–90. doi:10.1128/MCB.21.10.3482-3490.2001. ISSN 0270-7306. PMID 11313474.  
  10. ^ Malek, S; Huxford T, Ghosh G (Sep. 1998). "Ikappa Balpha functions through direct contacts with the nuclear localization signals and the DNA binding sequences of NF-kappaB". J. Biol. Chem. (UNITED STATES) 273 (39): 25427–35. ISSN 0021-9258. PMID 9738011.  
  11. ^ a b c d Bouwmeester, Tewis; Bauch Angela, Ruffner Heinz, Angrand Pierre-Olivier, Bergamini Giovanna, Croughton Karen, Cruciat Cristina, Eberhard Dirk, Gagneur Julien, Ghidelli Sonja, Hopf Carsten, Huhse Bettina, Mangano Raffaella, Michon Anne-Marie, Schirle Markus, Schlegl Judith, Schwab Markus, Stein Martin A, Bauer Andreas, Casari Georg, Drewes Gerard, Gavin Anne-Claude, Jackson David B, Joberty Gerard, Neubauer Gitte, Rick Jens, Kuster Bernhard, Superti-Furga Giulio (Feb. 2004). "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nat. Cell Biol. (England) 6 (2): 97–105. doi:10.1038/ncb1086. ISSN 1465-7392. PMID 14755267.  
  12. ^ Palvimo, J J; Reinikainen P, Ikonen T, Kallio P J, Moilanen A, Jänne O A (Sep. 1996). "Mutual transcriptional interference between RelA and androgen receptor". J. Biol. Chem. (UNITED STATES) 271 (39): 24151–6. ISSN 0021-9258. PMID 8798655.  
  13. ^ Ayroldi, E; Migliorati G, Bruscoli S, Marchetti C, Zollo O, Cannarile L, D'Adamio F, Riccardi C (Aug. 2001). "Modulation of T-cell activation by the glucocorticoid-induced leucine zipper factor via inhibition of nuclear factor kappaB". Blood (United States) 98 (3): 743–53. ISSN 0006-4971. PMID 11468175.  
  14. ^ Guan, E; Wang J, Laborda J, Norcross M, Baeuerle P A, Hoffman T (May. 1996). "T cell leukemia-associated human Notch/translocation-associated Notch homologue has I kappa B-like activity and physically interacts with nuclear factor-kappa B proteins in T cells". J. Exp. Med. (UNITED STATES) 183 (5): 2025–32. ISSN 0022-1007. PMID 8642313.  
  15. ^ Wang, J; Shelly L, Miele L, Boykins R, Norcross M A, Guan E (Jul. 2001). "Human Notch-1 inhibits NF-kappa B activity in the nucleus through a direct interaction involving a novel domain". J. Immunol. (United States) 167 (1): 289–95. ISSN 0022-1767. PMID 11418662.  
  16. ^ Zhong, Haihong; May Michael J, Jimi Eijiro, Ghosh Sankar (Mar. 2002). "The phosphorylation status of nuclear NF-kappa B determines its association with CBP/p300 or HDAC-1". Mol. Cell (United States) 9 (3): 625–36. ISSN 1097-2765. PMID 11931769.  
  17. ^ Ferrier, R; Nougarede R, Doucet S, Kahn-Perles B, Imbert J, Mathieu-Mahul D (Jan. 1999). "Physical interaction of the bHLH LYL1 protein and NF-kappaB1 p105". Oncogene (ENGLAND) 18 (4): 995–1005. doi:10.1038/sj.onc.1202374. ISSN 0950-9232. PMID 10023675.  
  18. ^ Thornburg, Natalie J; Pathmanathan Rajadurai, Raab-Traub Nancy (Dec. 2003). "Activation of nuclear factor-kappaB p50 homodimer/Bcl-3 complexes in nasopharyngeal carcinoma". Cancer Res. (United States) 63 (23): 8293–301. ISSN 0008-5472. PMID 14678988.  
  19. ^ Naumann, M; Wulczyn F G, Scheidereit C (Jan. 1993). "The NF-kappa B precursor p105 and the proto-oncogene product Bcl-3 are I kappa B molecules and control nuclear translocation of NF-kappa B". EMBO J. (ENGLAND) 12 (1): 213–22. ISSN 0261-4189. PMID 8428580.  
  20. ^ Yu, Zhiyuan; Zhang Wenzheng, Kone Bruce C (Oct. 2002). "Signal transducers and activators of transcription 3 (STAT3) inhibits transcription of the inducible nitric oxide synthase gene by interacting with nuclear factor kappaB". Biochem. J. (England) 367 (Pt 1): 97–105. doi:10.1042/BJ20020588. ISSN 0264-6021. PMID 12057007.  
  21. ^ Belich, M P; Salmerón A, Johnston L H, Ley S C (Jan. 1999). "TPL-2 kinase regulates the proteolysis of the NF-kappaB-inhibitory protein NF-kappaB1 p105". Nature (ENGLAND) 397 (6717): 363–8. doi:10.1038/16946. ISSN 0028-0836. PMID 9950430.  
  22. ^ Heppner, C; Bilimoria K Y, Agarwal S K, Kester M, Whitty L J, Guru S C, Chandrasekharappa S C, Collins F S, Spiegel A M, Marx S J, Burns A L (Aug. 2001). "The tumor suppressor protein menin interacts with NF-kappaB proteins and inhibits NF-kappaB-mediated transactivation". Oncogene (England) 20 (36): 4917–25. doi:10.1038/sj.onc.1204529. ISSN 0950-9232. PMID 11526476.  
  23. ^ Lee, S K; Na S Y, Jung S Y, Choi J E, Jhun B H, Cheong J, Meltzer P S, Lee Y C, Lee J W (Jun. 2000). "Activating protein-1, nuclear factor-kappaB, and serum response factor as novel target molecules of the cancer-amplified transcription coactivator ASC-2". Mol. Endocrinol. (UNITED STATES) 14 (6): 915–25. ISSN 0888-8809. PMID 10847592.  
  24. ^ Na, S Y; Lee S K, Han S J, Choi H S, Im S Y, Lee J W (May. 1998). "Steroid receptor coactivator-1 interacts with the p50 subunit and coactivates nuclear factor kappaB-mediated transactivations". J. Biol. Chem. (UNITED STATES) 273 (18): 10831–4. ISSN 0021-9258. PMID 9556555.  
  25. ^ Noro, Barbara; Licheri Barbara, Sgarra Riccardo, Rustighi Alessandra, Tessari Michela A, Chau Kai-Yin, Ono Santa Jeremy, Giancotti Vincenzo, Manfioletti Guidalberto (Apr. 2003). "Molecular dissection of the architectural transcription factor HMGA2". Biochemistry (United States) 42 (15): 4569–77. doi:10.1021/bi026605k. ISSN 0006-2960. PMID 12693954.  

Further reading

  • Baldwin AS (1996). "The NF-kappa B and I kappa B proteins: new discoveries and insights.". Annu. Rev. Immunol. 14: 649–83. doi:10.1146/annurev.immunol.14.1.649. PMID 8717528.  
  • Snásel J, Pichová I (1997). "The cleavage of host cell proteins by HIV-1 protease.". Folia Biol. (Praha) 42 (5): 227–30. PMID 8997639.  
  • Chen F, Castranova V, Shi X, Demers LM (1999). "New insights into the role of nuclear factor-kappaB, a ubiquitous transcription factor in the initiation of diseases.". Clin. Chem. 45 (1): 7–17. PMID 9895331.  
  • Bottex-Gauthier C, Pollet S, Favier A, Vidal DR (2002). "[The Rel/NF-kappa-B transcription factors: complex role in cell regulation]". Pathol. Biol. 50 (3): 204–11. PMID 11980335.  
  • Garg A, Aggarwal BB (2002). "Nuclear transcription factor-kappaB as a target for cancer drug development.". Leukemia 16 (6): 1053–68. doi:10.1038/sj.leu.2402482. PMID 12040437.  
  • Sun Z, Andersson R (2003). "NF-kappaB activation and inhibition: a review.". Shock 18 (2): 99–106. doi:10.1097/00024382-200208000-00001. PMID 12166787.  
  • Mercurio AM (2003). "Invasive skin carcinoma--Ras and alpha6beta4 integrin lead the way.". Cancer Cell 3 (3): 201–2. doi:10.1016/S1535-6108(03)00049-7. PMID 12676577.  
  • Sun SC, Xiao G (2004). "Deregulation of NF-kappaB and its upstream kinases in cancer.". Cancer Metastasis Rev. 22 (4): 405–22. doi:10.1023/A:1023733231406. PMID 12884915.  
  • Kucharczak J, Simmons MJ, Fan Y, Gélinas C (2004). "To be, or not to be: NF-kappaB is the answer--role of Rel/NF-kappaB in the regulation of apoptosis.". Oncogene 22 (56): 8961–82. doi:10.1038/sj.onc.1207230. PMID 14663476.  
  • Suh J, Rabson AB (2004). "NF-kappaB activation in human prostate cancer: important mediator or epiphenomenon?". J. Cell. Biochem. 91 (1): 100–17. doi:10.1002/jcb.10729. PMID 14689584.  
  • Muthumani K, Desai BM, Hwang DS, et al. (2004). "HIV-1 Vpr and anti-inflammatory activity.". DNA Cell Biol. 23 (4): 239–47. doi:10.1089/104454904773819824. PMID 15142381.  
  • Schmitz ML, Mattioli I, Buss H, Kracht M (2005). "NF-kappaB: a multifaceted transcription factor regulated at several levels.". Chembiochem 5 (10): 1348–58. doi:10.1002/cbic.200400144. PMID 15457532.  
  • Pise-Masison CA, Brady JN (2006). "Setting the stage for transformation: HTLV-1 Tax inhibition of p53 function.". Front. Biosci. 10: 919–30. doi:10.2741/1586. PMID 15569630.  
  • Joseph AM, Kumar M, Mitra D (2005). "Nef: "necessary and enforcing factor" in HIV infection.". Curr. HIV Res. 3 (1): 87–94. doi:10.2174/1570162052773013. PMID 15638726.  
  • Le Rouzic E, Benichou S (2006). "The Vpr protein from HIV-1: distinct roles along the viral life cycle.". Retrovirology 2: 11. doi:10.1186/1742-4690-2-11. PMID 15725353.  
  • Zhao RY, Elder RT (2005). "Viral infections and cell cycle G2/M regulation.". Cell Res. 15 (3): 143–9. doi:10.1038/sj.cr.7290279. PMID 15780175.  
  • Zhao RY, Bukrinsky M, Elder RT (2005). "HIV-1 viral protein R (Vpr) & host cellular responses.". Indian J. Med. Res. 121 (4): 270–86. PMID 15817944.  
  • Muthumani K, Choo AY, Hwang DS, et al. (2006). "HIV-1 Vpr: enhancing sensitivity of tumors to apoptosis.". Current drug delivery 1 (4): 335–44. doi:10.2174/1567201043334614. PMID 16305395.  
  • Courtois G, Smahi A (2006). "NF-kappaB-related genetic diseases.". Cell Death Differ. 13 (5): 843–51. doi:10.1038/sj.cdd.4401841. PMID 16397577.  
  • Mattson MP, Meffert MK (2006). "Roles for NF-kappaB in nerve cell survival, plasticity, and disease.". Cell Death Differ. 13 (5): 852–60. doi:10.1038/sj.cdd.4401837. PMID 16397579.  
  • Schmitz ML, Krappmann D (2006). "Controlling NF-kappaB activation in T cells by costimulatory receptors.". Cell Death Differ. 13 (5): 834–42. doi:10.1038/sj.cdd.4401845. PMID 16410801.  
  • Janssens S, Tschopp J (2006). "Signals from within: the DNA-damage-induced NF-kappaB response.". Cell Death Differ. 13 (5): 773–84. doi:10.1038/sj.cdd.4401843. PMID 16410802.  
  • Perkins ND, Gilmore TD (2006). "Good cop, bad cop: the different faces of NF-kappaB.". Cell Death Differ. 13 (5): 759–72. doi:10.1038/sj.cdd.4401838. PMID 16410803.  
  • Weil R, Israël A (2006). "Deciphering the pathway from the TCR to NF-kappaB.". Cell Death Differ. 13 (5): 826–33. doi:10.1038/sj.cdd.4401856. PMID 16439988.  
  • Kim HJ, Hawke N, Baldwin AS (2006). "NF-kappaB and IKK as therapeutic targets in cancer.". Cell Death Differ. 13 (5): 738–47. doi:10.1038/sj.cdd.4401877. PMID 16485028.  
  • Braun T, Carvalho G, Fabre C, et al. (2006). "Targeting NF-kappaB in hematologic malignancies.". Cell Death Differ. 13 (5): 748–58. doi:10.1038/sj.cdd.4401874. PMID 16498458.  
  • Bottero V, Withoff S, Verma IM (2006). "NF-kappaB and the regulation of hematopoiesis.". Cell Death Differ. 13 (5): 785–97. doi:10.1038/sj.cdd.4401888. PMID 16528384.  
  • Xiao G (2007). "Autophagy and NF-kappaB: fight for fate.". Cytokine Growth Factor Rev. 18 (3-4): 233–43. doi:10.1016/j.cytogfr.2007.04.006. PMID 17485237.  

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