BCL11B

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BCL11B
Identifiers
AliasesBCL11B, ATL1, ATL1-alpha, ATL1-beta, ATL1-delta, ATL1-gamma, CTIP-2, CTIP2, RIT1, ZNF856B, hRIT1-alpha, B-cell CLL/lymphoma 11B, IMD49, B cell CLL/lymphoma 11B, IDDFSTA, BAF complex component, BAF chromatin remodeling complex subunit BCL11B
External IDsOMIM: 606558 MGI: 1929913 HomoloGene: 10974 GeneCards: BCL11B
Gene location (Human)
Chromosome 14 (human)
Chr.Chromosome 14 (human)[1]
Chromosome 14 (human)
Genomic location for BCL11B
Genomic location for BCL11B
Band14q32.2Start99,169,287 bp[1]
End99,272,197 bp[1]
RNA expression pattern
PBB GE BCL11B 219528 s at fs.png
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001282237
NM_001282238
NM_022898
NM_138576

NM_001079883
NM_001286343
NM_021399

RefSeq (protein)

NP_001269166
NP_001269167
NP_075049
NP_612808

NP_001073352
NP_001273272
NP_067374

Location (UCSC)Chr 14: 99.17 – 99.27 MbChr 12: 107.91 – 108 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

B-cell lymphoma/leukemia 11B is a protein that in humans is encoded by the BCL11B gene.[5][6][7]

Gene location[edit]

BCL11B is located on human chromosome 14p32.2.[8] The mouse analogue is called Rit1 or Bcl11b and is located on mouse chormosome 12.[9]

Function[edit]

This gene encodes a C2H2-type zinc finger protein and is closely related to BCL11A, a gene whose translocation may be associated with B-cell malignancies. The specific function of this gene has not yet been determined, but it could also be involved in some malignancies. Two alternatively spliced transcript variants, which encode distinct isoforms, have been reported.[7]

Recent research suggests that BCL11B is crucial for ameloblasts (the cells that produce tooth enamel) to form and work properly.[10]

Interactions[edit]

BCL11B has been shown to interact with COUP-TFI.[11]

Pathology[edit]

BCL11B is closely connected with immune regulation and for so its mutation can lead to a SCID phenotype. This so-called Immunodeficiency 49 (OMIM #617237) is classified as T-B+NK+ SCID.[12] It is characterised by a lack of T lymphocytes and its malfunctioning specifically in proliferative response. On the other hand, B cells and NK cells counts and functions are not impaired.[13] The symptoms of SCID caused by BCL11B mutation - apart from immunity defects - typically include teeth abnormalities, craniofacial dimorphism, different types of dermatitis. As well the intellectual development is significantly impaired. The disease has a very early onset and the only known treatment is hematopoietic stem cell transplantation from a healthy donor.[14][13] The immunodeficiency has a dominant negative mode of inheritance as all so far described patients suffering from it has been after sequencing identified as heterozygotes in the BCL11B gene.[13][14]

Research projects[edit]

A mouse model based study showed, that Bcl11b also plays an important role in pathogenesis of inflammatory bowel disease. Bcl11b gene knock-out in certain T cell population led to development of IBD. The mechanisms behind are supposed to be reduced suppressor activity of T regulatory cells and changes in cytokine environment. Bcl11b is suspected to interact with Foxp3 and IL10 gene promoters and thus impair its suppressive function in the intestines.[15]

Bcl11b (mouse analogue of human BCL11B) has been proven to contribute to malignant growth for example in case of mouse lymphomas. That is suspected to be caused by interaction with p53, a well-known tumor suppressor gene.[9]

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000127152 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000048251 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Satterwhite E, Sonoki T, Willis TG, Harder L, Nowak R, Arriola EL, et al. (December 2001). "The BCL11 gene family: involvement of BCL11A in lymphoid malignancies". Blood. 98 (12): 3413–20. doi:10.1182/blood.V98.12.3413. PMID 11719382.
  6. ^ Topark-Ngarm A, Golonzhka O, Peterson VJ, Barrett B, Martinez B, Crofoot K, et al. (October 2006). "CTIP2 associates with the NuRD complex on the promoter of p57KIP2, a newly identified CTIP2 target gene". The Journal of Biological Chemistry. 281 (43): 32272–83. doi:10.1074/jbc.M602776200. PMC 2547407. PMID 16950772.
  7. ^ a b "Entrez Gene: BCL11B B-cell CLL/lymphoma 11B (zinc finger protein)".
  8. ^ "OMIM Entry - * 606558 - B-CELL CLL/LYMPHOMA 11B; BCL11B". www.omim.org. Retrieved 2019-07-29.
  9. ^ a b Wakabayashi Y, Inoue J, Takahashi Y, Matsuki A, Kosugi-Okano H, Shinbo T, et al. (February 2003). "Homozygous deletions and point mutations of the Rit1/Bcl11b gene in gamma-ray induced mouse thymic lymphomas". Biochemical and Biophysical Research Communications. 301 (2): 598–603. doi:10.1016/S0006-291X(02)03069-3. PMID 12565905.
  10. ^ Golonzhka O, Metzger D, Bornert JM, Bay BK, Gross MK, Kioussi C, Leid M (March 2009). "Ctip2/Bcl11b controls ameloblast formation during mammalian odontogenesis". Proceedings of the National Academy of Sciences of the United States of America. 106 (11): 4278–83. Bibcode:2009PNAS..106.4278G. doi:10.1073/pnas.0900568106. PMC 2657370. PMID 19251658. Lay summaryBBC News.
  11. ^ Avram D, Fields A, Pretty On Top K, Nevrivy DJ, Ishmael JE, Leid M (April 2000). "Isolation of a novel family of C(2)H(2) zinc finger proteins implicated in transcriptional repression mediated by chicken ovalbumin upstream promoter transcription factor (COUP-TF) orphan nuclear receptors". The Journal of Biological Chemistry. 275 (14): 10315–22. doi:10.1074/jbc.275.14.10315. PMC 2819356. PMID 10744719.
  12. ^ Advances in immunology. Volume 138. Alt, Frederick W. Cambridge, MA. ISBN 9780128155295. OCLC 1035016036.CS1 maint: others (link)
  13. ^ a b c Punwani D, Zhang Y, Yu J, Cowan MJ, Rana S, Kwan A, et al. (December 2016). "Multisystem Anomalies in Severe Combined Immunodeficiency with Mutant BCL11B". The New England Journal of Medicine. 375 (22): 2165–2176. doi:10.1056/nejmoa1509164. PMC 5215776. PMID 27959755.
  14. ^ a b Lessel D, Gehbauer C, Bramswig NC, Schluth-Bolard C, Venkataramanappa S, van Gassen KL, et al. (August 2018). "BCL11B mutations in patients affected by a neurodevelopmental disorder with reduced type 2 innate lymphoid cells". Brain. 141 (8): 2299–2311. doi:10.1093/brain/awy173. PMC 6061686. PMID 29985992.
  15. ^ Vanvalkenburgh J, Albu DI, Bapanpally C, Casanova S, Califano D, Jones DM, et al. (September 2011). "Critical role of Bcl11b in suppressor function of T regulatory cells and prevention of inflammatory bowel disease". The Journal of Experimental Medicine. 208 (10): 2069–81. doi:10.1084/jem.20102683. PMC 3182057. PMID 21875956.

Further reading[edit]

External links[edit]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.