CIITA
{{Short description|Protein-coding gene in humans}}
{{Infobox_gene}}
CIITA is a human gene which encodes a protein called the class II, major histocompatibility complex, transactivator.{{cite journal | vauthors = Steimle V, Otten LA, Zufferey M, Mach B | title = Complementation cloning of an MHC class II transactivator mutated in hereditary MHC class II deficiency (or bare lymphocyte syndrome) | journal = Cell | volume = 75 | issue = 1 | pages = 135–46 | date = Oct 1993 | pmid = 8402893 | doi = 10.1016/S0092-8674(05)80090-X | s2cid = 30276144 }} Mutations in this gene are responsible for the bare lymphocyte syndrome in which the immune system is severely compromised and cannot effectively fight infection. Chromosomal rearrangement of CIITA is involved in the pathogenesis of Hodgkin lymphoma and primary mediastinal B cell lymphoma.{{cite journal | vauthors = Steidl C, Shah SP, Woolcock BW, Rui L, Kawahara M, Farinha P, Johnson NA, Zhao Y, Telenius A, Neriah SB, McPherson A, Meissner B, Okoye UC, Diepstra A, van den Berg A, Sun M, Leung G, Jones SJ, Connors JM, Huntsman DG, Savage KJ, Rimsza LM, Horsman DE, Staudt LM, Steidl U, Marra MA, Gascoyne RD | title = MHC class II transactivator CIITA is a recurrent gene fusion partner in lymphoid cancers | journal = Nature | volume = 471 | issue = 7338 | pages = 377–81 | date = Mar 2011 | pmid = 21368758 | pmc = 3902849 | doi = 10.1038/nature09754 | bibcode = 2011Natur.471..377S }}
Function
CIITA mRNA can only be detected in human leukocyte antigen (HLA) system class II-positive cell lines and tissues. This highly restricted tissue distribution suggests that expression of HLA class II genes is to a large extent under the control of CIITA.{{cite journal | vauthors = Mach B, Steimle V, Reith W | title = MHC class II-deficient combined immunodeficiency: a disease of gene regulation | journal = Immunological Reviews | volume = 138 | issue = 1 | pages = 207–21 | date = Apr 1994 | pmid = 8070816 | doi = 10.1111/j.1600-065X.1994.tb00853.x | s2cid = 28869787 }} However, CIITA does not appear to directly bind to DNA. Instead CIITA functions through activation of the transcription factor RFX5.{{cite journal | vauthors = Scholl T, Mahanta SK, Strominger JL | title = Specific complex formation between the type II bare lymphocyte syndrome-associated transactivators CIITA and RFX5 | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 94 | issue = 12 | pages = 6330–4 | date = Jun 1997 | pmid = 9177217 | pmc = 21049 | doi = 10.1073/pnas.94.12.6330 | bibcode = 1997PNAS...94.6330S | doi-access = free }} Hence CIITA is classified as a transcriptional coactivator.
The CIITA protein contains an acidic transcriptional activation domain, 4 LRRs (leucine-rich repeats) and a GTP binding domain.{{cite journal | vauthors = Raval A, Howcroft TK, Weissman JD, Kirshner S, Zhu XS, Yokoyama K, Ting J, Singer DS | title = Transcriptional coactivator, CIITA, is an acetyltransferase that bypasses a promoter requirement for TAF(II)250 | journal = Molecular Cell | volume = 7 | issue = 1 | pages = 105–15 | date = Jan 2001 | pmid = 11172716 | doi = 10.1016/S1097-2765(01)00159-9 | doi-access = free }} The protein uses GTP binding to facilitate its own transport into the nucleus.{{cite journal | vauthors = Harton JA, Cressman DE, Chin KC, Der CJ, Ting JP | title = GTP binding by class II transactivator: role in nuclear import | journal = Science | volume = 285 | issue = 5432 | pages = 1402–5 | date = Aug 1999 | pmid = 10464099 | doi = 10.1126/science.285.5432.1402 }} Once in the nucleus, the protein acts as a positive regulator of class II major histocompatibility complex gene transcription, and is often referred to as the "master control factor" for the expression of these genes.{{cite journal | vauthors = Harton JA, Ting JP | title = Class II transactivator: mastering the art of major histocompatibility complex expression | journal = Molecular and Cellular Biology | volume = 20 | issue = 17 | pages = 6185–94 | date = Sep 2000 | pmid = 10938095 | pmc = 86093 | doi = 10.1128/MCB.20.17.6185-6194.2000 }}{{cite journal | vauthors = LeibundGut-Landmann S, Waldburger JM, Krawczyk M, Otten LA, Suter T, Fontana A, Acha-Orbea H, Reith W | title = Mini-review: Specificity and expression of CIITA, the master regulator of MHC class II genes | journal = European Journal of Immunology | volume = 34 | issue = 6 | pages = 1513–25 | date = Jun 2004 | pmid = 15162420 | doi = 10.1002/eji.200424964 | s2cid = 21226976 | doi-access = free }}
CIITA expression is induced by interferon gamma, possibly assisted by other signals.{{cite journal | vauthors = Heuberger C, Pott J, Maloy KJ | title = Why do intestinal epithelial cells express MHC class II? | journal = Immunology | volume = 162 | issue=4 | pages = 357–367 |date=2021 | doi = 10.1111/imm.13270 | pmc =7968399 | pmid = 32966619}} MHC II expression in intestinal epithelial cells is upregulated under inflammation.
Interactions
CIITA has been shown to interact with:
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- MAPK1,{{cite journal | vauthors = Voong LN, Slater AR, Kratovac S, Cressman DE | title = Mitogen-activated protein kinase ERK1/2 regulates the class II transactivator | journal = The Journal of Biological Chemistry | volume = 283 | issue = 14 | pages = 9031–9 | date = Apr 2008 | pmid = 18245089 | pmc = 2431044 | doi = 10.1074/jbc.M706487200 | doi-access = free }}
- Nuclear receptor coactivator 1,{{cite journal | vauthors = Tzortzakaki E, Spilianakis C, Zika E, Kretsovali A, Papamatheakis J | title = Steroid receptor coactivator 1 links the steroid and interferon gamma response pathways | journal = Molecular Endocrinology | volume = 17 | issue = 12 | pages = 2509–18 | date = Dec 2003 | pmid = 12933903 | doi = 10.1210/me.2002-0439 | doi-access = free }}
- RFX5,{{cite journal | vauthors = Hake SB, Masternak K, Kammerbauer C, Janzen C, Reith W, Steimle V | title = CIITA leucine-rich repeats control nuclear localization, in vivo recruitment to the major histocompatibility complex (MHC) class II enhanceosome, and MHC class II gene transactivation | journal = Molecular and Cellular Biology | volume = 20 | issue = 20 | pages = 7716–25 | date = Oct 2000 | pmid = 11003667 | pmc = 86349 | doi = 10.1128/mcb.20.20.7716-7725.2000}}
- RFXANK,{{cite journal | vauthors = Nekrep N, Geyer M, Jabrane-Ferrat N, Peterlin BM | title = Analysis of ankyrin repeats reveals how a single point mutation in RFXANK results in bare lymphocyte syndrome | journal = Molecular and Cellular Biology | volume = 21 | issue = 16 | pages = 5566–76 | date = Aug 2001 | pmid = 11463838 | pmc = 87278 | doi = 10.1128/MCB.21.16.5566-5576.2001 }}
- XPO1,{{cite journal | vauthors = Raval A, Weissman JD, Howcroft TK, Singer DS | title = The GTP-binding domain of class II transactivator regulates its nuclear export | journal = Journal of Immunology | volume = 170 | issue = 2 | pages = 922–30 | date = Jan 2003 | pmid = 12517958 | doi = 10.4049/jimmunol.170.2.922| doi-access = free }} and
- ZXDC.{{cite journal | vauthors = Al-Kandari W, Jambunathan S, Navalgund V, Koneni R, Freer M, Parimi N, Mudhasani R, Fontes JD | title = ZXDC, a novel zinc finger protein that binds CIITA and activates MHC gene transcription | journal = Molecular Immunology | volume = 44 | issue = 4 | pages = 311–21 | date = Jan 2007 | pmid = 16600381 | pmc = 1624858 | doi = 10.1016/j.molimm.2006.02.029 }}{{cite journal | vauthors = Al-Kandari W, Koneni R, Navalgund V, Aleksandrova A, Jambunathan S, Fontes JD | title = The zinc finger proteins ZXDA and ZXDC form a complex that binds CIITA and regulates MHC II gene transcription | journal = Journal of Molecular Biology | volume = 369 | issue = 5 | pages = 1175–87 | date = Jun 2007 | pmid = 17493635 | pmc = 1963517 | doi = 10.1016/j.jmb.2007.04.033 }}
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See also
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References
{{Reflist|33em}}
External links
- {{MeshName|MHC+class+II+transactivator+protein}}
- {{UCSC gene info|CIITA}}
{{NLM content}}
{{gene-16-stub}}