NFKB1

From Wikipedia, the free encyclopedia
Jump to: navigation, search
Nuclear factor of kappa light polypeptide gene enhancer in B-cells 1
Protein NFKB1 PDB 1bfs.png
PDB rendering based on 1bfs.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols NFKB1 ; EBP-1; KBF1; NF-kB1; NF-kappa-B; NF-kappaB; NFKB-p105; NFKB-p50; NFkappaB; p105; p50
External IDs OMIM164011 MGI97312 HomoloGene2971 ChEMBL: 3251 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 NM_008689
RefSeq (protein) NP_001158884 NP_032715
Location (UCSC) Chr 4:
103.42 – 103.54 Mb
Chr 3:
135.58 – 135.69 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]

Model organisms[edit]

Model organisms have been used in the study of NFKB1 function. A conditional knockout mouse line, called Nfkb1tm1a(KOMP)Wtsi[10][11] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[12][13][14]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[8][15] Twenty five tests were carried out on mutant mice and six significant abnormalities were observed.[8] Female homozygotes had a decreased respiratory quotient, increased circulating alkaline phosphatase level and increased leukocyte cell number. Male homozygotes showed an increased susceptibility to Salmonella infection, while homozygotes of both sex had decreased IgG1 and decreased regulatory T cell and NK cell numbers.[8]

Interactions[edit]

NFKB1 has been shown to interact with NFKBIE,[16] IKK2,[17][18] MAP3K7IP2,[19] STAT6,[20] ITGB3BP,[21] IκBα,[22][23] NFKB2,[24] RELA,[24][25] RELB,[24] TSC22D3,[26] NOTCH1,[27][28] HDAC1,[29] LYL1,[30] BCL3,[18][31][32] STAT3,[33] MAP3K8,[24][34] MEN1,[35] Nuclear receptor coactivator 1,[36][37] HMGA2[38] and C22orf25.[39]

References[edit]

  1. ^ Meyer R, Hatada EN, Hohmann HP, Haiker M, Bartsch C, Rothlisberger U, Lahm HW, Schlaeger EJ, van Loon AP, Scheidereit C (March 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. 
  2. ^ "Entrez Gene: NF-κB nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)". 
  3. ^ "Eye morphology data for Nfkb1". Wellcome Trust Sanger Institute. 
  4. ^ "Clinical chemistry data for Nfkb1". Wellcome Trust Sanger Institute. 
  5. ^ "Haematology data for Nfkb1". Wellcome Trust Sanger Institute. 
  6. ^ "Peripheral blood lymphocytes data for Nfkb1". Wellcome Trust Sanger Institute. 
  7. ^ "Salmonella infection data for Nfkb1". Wellcome Trust Sanger Institute. 
  8. ^ a b c d Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x. 
  9. ^ Mouse Resources Portal, Wellcome Trust Sanger Institute.
  10. ^ "International Knockout Mouse Consortium". 
  11. ^ "Mouse Genome Informatics". 
  12. ^ Skarnes, W. C.; Rosen, B.; West, A. P.; Koutsourakis, M.; Bushell, W.; Iyer, V.; Mujica, A. O.; Thomas, M.; Harrow, J.; Cox, T.; Jackson, D.; Severin, J.; Biggs, P.; Fu, J.; Nefedov, M.; De Jong, P. J.; Stewart, A. F.; Bradley, A. (2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337–342. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.  edit
  13. ^ Dolgin E (2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718. 
  14. ^ Collins FS, Rossant J, Wurst W (2007). "A Mouse for All Reasons". Cell 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247. 
  15. ^ van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism.". Genome Biol 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353. 
  16. ^ Li, Z; Nabel G J (October 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. 
  17. ^ Heissmeyer, V; Krappmann D; Hatada E N; Scheidereit C (February 2001). "Shared Pathways of IκB Kinase-Induced SCFβTrCP-Mediated Ubiquitination and Degradation for the NF-κB Precursor p105 and IκBα". 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. 
  18. ^ a b Heissmeyer, V; Krappmann D; Wulczyn F G; Scheidereit C (September 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. 
  19. ^ Baek, Sung Hee; Ohgi Kenneth A; Rose David W; Koo Edward H; Glass Christopher K; Rosenfeld Michael G (July 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. 
  20. ^ Shen, C H; Stavnezer J (June 1998). "Interaction of Stat6 and NF-κB: 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. 
  21. ^ Besta, Felicitas; Massberg Steffen, Brand Korbinian, Müller Elke, Page Sharon, Grüner Sabine, Lorenz Michael, Sadoul Karin, Kolanus Waldemar, Lengyel Ernst, Gawaz Meinrad (October 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. 
  22. ^ Hay, D C; Kemp G D; Dargemont C; Hay R T (May 2001). "Interaction between hnRNPA1 and IκBα Is Required for Maximal Activation of NF-κB-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. 
  23. ^ Malek, S; Huxford T; Ghosh G (September 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. 
  24. ^ 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 (February 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. 
  25. ^ Palvimo, J J; Reinikainen P; Ikonen T; Kallio P J; Moilanen A; Jänne O A (September 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. 
  26. ^ Ayroldi, E; Migliorati G; Bruscoli S; Marchetti C; Zollo O; Cannarile L; D'Adamio F; Riccardi C (August 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. 
  27. ^ 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. 
  28. ^ Wang, J; Shelly L; Miele L; Boykins R; Norcross M A; Guan E (July 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. doi:10.4049/jimmunol.167.1.289. ISSN 0022-1767. PMID 11418662. 
  29. ^ Zhong, Haihong; May Michael J; Jimi Eijiro; Ghosh Sankar (March 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. 
  30. ^ Ferrier, R; Nougarede R; Doucet S; Kahn-Perles B; Imbert J; Mathieu-Mahul D (January 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. 
  31. ^ Thornburg, Natalie J; Pathmanathan Rajadurai, Raab-Traub Nancy (December 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. 
  32. ^ Naumann, M; Wulczyn F G; Scheidereit C (January 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. 
  33. ^ Yu, Zhiyuan; Zhang Wenzheng; Kone Bruce C (October 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. 
  34. ^ Belich, M P; Salmerón A; Johnston L H; Ley S C (January 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. 
  35. ^ 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 (August 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. 
  36. ^ 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 (June 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/mend.14.6.0471. ISSN 0888-8809. PMID 10847592. 
  37. ^ 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. 
  38. ^ Noro, Barbara; Licheri Barbara; Sgarra Riccardo; Rustighi Alessandra; Tessari Michela A; Chau Kai-Yin; Ono Santa Jeremy; Giancotti Vincenzo; Manfioletti Guidalberto (April 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. 
  39. ^ "Molecular Interaction Database". 

Further reading[edit]

External links[edit]