Biology:BCL11B

Short description: Protein-coding gene in the species Homo sapiens

Generic protein structure example

B-cell lymphoma/leukemia 11B is a protein that in humans is encoded by the BCL11B gene.

Gene location

BCL11B is located on human chromosome 14p32.2. The mouse analogue is called Rit1 or Bcl11b and is located on mouse chromosome 12.

Function

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.

Research suggests that BCL11B is crucial for ameloblasts (the cells that produce tooth enamel) to form and work properly.

Interactions

BCL11B has been shown to interact with COUP-TFI.

Pathology

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. 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. 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. The immunodeficiency has a dominant negative mode of inheritance as all so far described patients with it has been after sequencing identified as heterozygotes in the BCL11B gene.

Research projects

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.

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.

Further reading

• "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. April 2000. doi:10.1074/jbc.275.14.10315. PMID 10744719. 
• "COUP-TF (chicken ovalbumin upstream promoter transcription factor)-interacting protein 1 (CTIP1) is a sequence-specific DNA binding protein". The Biochemical Journal 368 (Pt 2): 555–63. December 2002. doi:10.1042/BJ20020496. PMID 12196208. 
• "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. February 2003. doi:10.1016/S0006-291X(02)03069-3. PMID 12565905. 
• "Recruitment of Tat to heterochromatin protein HP1 via interaction with CTIP2 inhibits human immunodeficiency virus type 1 replication in microglial cells". Journal of Virology 77 (9): 5415–27. May 2003. doi:10.1128/JVI.77.9.5415-5427.2003. PMID 12692243. 
• "Involvement of the histone deacetylase SIRT1 in chicken ovalbumin upstream promoter transcription factor (COUP-TF)-interacting protein 2-mediated transcriptional repression". The Journal of Biological Chemistry 278 (44): 43041–50. October 2003. doi:10.1074/jbc.M307477200. PMID 12930829. 
• "A novel t(6;14)(q25-q27;q32) in acute myelocytic leukemia involves the BCL11B gene". Cancer Genetics and Cytogenetics 149 (1): 72–6. February 2004. doi:10.1016/S0165-4608(03)00302-9. PMID 15104287. 
• "BCL11B rearrangements probably target T-cell neoplasia rather than acute myelocytic leukemia". Cancer Genetics and Cytogenetics 153 (1): 88–9. August 2004. doi:10.1016/j.cancergencyto.2004.02.020. PMID 15325104. 
• "Disruption of the BCL11B gene through inv(14)(q11.2q32.31) results in the expression of BCL11B-TRDC fusion transcripts and is associated with the absence of wild-type BCL11B transcripts in T-ALL". Leukemia 19 (2): 201–8. February 2005. doi:10.1038/sj.leu.2403619. PMID 15668700. 
• "BCL11B functionally associates with the NuRD complex in T lymphocytes to repress targeted promoter". Oncogene 24 (45): 6753–64. October 2005. doi:10.1038/sj.onc.1208904. PMID 16091750. 
• "Recruitment of chromatin-modifying enzymes by CTIP2 promotes HIV-1 transcriptional silencing". The EMBO Journal 26 (2): 412–23. January 2007. doi:10.1038/sj.emboj.7601516. PMID 17245431. 
• "Activation of TLX3 and NKX2-5 in t(5;14)(q35;q32) T-cell acute lymphoblastic leukemia by remote 3'-BCL11B enhancers and coregulation by PU.1 and HMGA1". Cancer Research 67 (4): 1461–71. February 2007. doi:10.1158/0008-5472.CAN-06-2615. PMID 17308084. 
• "Lack of Bcl11b tumor suppressor results in vulnerability to DNA replication stress and damages". Oncogene 26 (40): 5840–50. August 2007. doi:10.1038/sj.onc.1210388. PMID 17369851. 

External links

• BCL11B+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
• Human ATL1 genome location and ATL1 gene details page in the UCSC Genome Browser.
• Human BCL11B genome location and BCL11B gene details page in the UCSC Genome Browser.
• Human RIT1 genome location and RIT1 gene details page in the UCSC Genome Browser.

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