NFKB1

NFKB1
Nuclear factor of kappa light polypeptide gene enhancer in B-cells 1

PDB rendering based on 1bfs.
Identifiers
Symbols NFKB1; DKFZp686C01211; EBP-1; KBF1; MGC54151; NF-kappa-B; NF-kappaB; NFKB-p105; NFKB-p50; p105; 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_001165412.1 NM_008689.2
RefSeq (protein) NP_001158884.1 NP_032715.2
Location (UCSC) Chr 4:
103.42 – 103.54 Mb
Chr 3:
135.25 – 135.35 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,[5][18][19] STAT3,[20] MAP3K8,[11][21] 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. doi:10.1073/pnas.88.3.966. PMC 50935. PMID 1992489. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=50935. 
  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. PMC 232469. PMID 9315679. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=232469. 
  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. PMC 99557. PMID 11158290. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=99557. 
  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. PMC 1171549. PMID 10469655. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1171549. 
  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. doi:10.1016/S0092-8674(02)00809-7. 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. PMC 108921. PMID 9584180. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=108921. 
  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. doi:10.1242/jcs.00081. 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. PMC 100270. PMID 11313474. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=100270. 
  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. doi:10.1074/jbc.273.39.25427. 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 14743216. 
  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. doi:10.1074/jbc.271.39.24151. 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. doi:10.1182/blood.V98.3.743. 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. doi:10.1084/jem.183.5.2025. ISSN 0022-1007. PMC 2192574. PMID 8642313. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2192574. 
  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. doi:10.1016/S1097-2765(02)00477-X. 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. PMC 413194. PMID 8428580. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=413194. 
  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. PMC 1222853. PMID 12057007. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1222853. 
  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. doi:10.1210/me.14.6.915. 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. doi:10.1074/jbc.273.18.10831. 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

External links


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