BCL11A: Difference between revisions

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{{Infobox_gene}}
{{PBB_Controls
'''B-cell lymphoma/leukemia 11A''' is a [[protein]] that in humans is encoded by the ''BCL11A'' [[gene]].<ref name="pmid11719382">{{cite journal | vauthors = Satterwhite E, Sonoki T, Willis TG, Harder L, Nowak R, Arriola EL, Liu H, Price HP, Gesk S, Steinemann D, Schlegelberger B, Oscier DG, Siebert R, Tucker PW, Dyer MJ | title = The BCL11 gene family: involvement of BCL11A in lymphoid malignancies | journal = Blood | volume = 98 | issue = 12 | pages = 3413–20 | date = December 2001 | pmid = 11719382 | pmc =  | doi = 10.1182/blood.V98.12.3413 }}</ref><ref name="pmid18245381">{{cite journal | vauthors = Uda M, Galanello R, Sanna S, Lettre G, Sankaran VG, Chen W, Usala G, Busonero F, Maschio A, Albai G, Piras MG, Sestu N, Lai S, Dei M, Mulas A, Crisponi L, Naitza S, Asunis I, Deiana M, Nagaraja R, Perseu L, Satta S, Cipollina MD, Sollaino C, Moi P, Hirschhorn JN, Orkin SH, Abecasis GR, Schlessinger D, Cao A | display-authors = 6 | title = Genome-wide association study shows BCL11A associated with persistent fetal hemoglobin and amelioration of the phenotype of beta-thalassemia | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 105 | issue = 5 | pages = 1620–5 | date = February 2008 | pmid = 18245381 | pmc = 2234194 | doi = 10.1073/pnas.0711566105 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: BCL11A B-cell CLL/lymphoma 11A (zinc finger protein)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=53335| access-date = }}</ref>
| update_page = yes
| require_manual_inspection = no
| update_protein_box = yes
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Function ==
{{GNF_Protein_box
| image =
| image_source =
| PDB =
| Name = B-cell CLL/lymphoma 11A (zinc finger protein)
| HGNCid = 13221
| Symbol = BCL11A
| AltSymbols =; BCL11A-L; BCL11A-S; BCL11A-XL; CTIP1; EVI9; FLJ10173; FLJ34997; KIAA1809
| OMIM = 606557
| ECnumber = 
| Homologene = 11284
| MGIid = 106190
| GeneAtlas_image1 = PBB_GE_BCL11A_219497_s_at_tn.png
| GeneAtlas_image2 = PBB_GE_BCL11A_219498_s_at_tn.png
| GeneAtlas_image3 = PBB_GE_BCL11A_210347_s_at_tn.png
| Function = {{GNF_GO|id=GO:0003676 |text = nucleic acid binding}} {{GNF_GO|id=GO:0003714 |text = transcription corepressor activity}} {{GNF_GO|id=GO:0008270 |text = zinc ion binding}} {{GNF_GO|id=GO:0046872 |text = metal ion binding}}
| Component = {{GNF_GO|id=GO:0005622 |text = intracellular}} {{GNF_GO|id=GO:0005634 |text = nucleus}} {{GNF_GO|id=GO:0005737 |text = cytoplasm}}
| Process = {{GNF_GO|id=GO:0006350 |text = transcription}} {{GNF_GO|id=GO:0006355 |text = regulation of transcription, DNA-dependent}} {{GNF_GO|id=GO:0030097 |text = hemopoiesis}} {{GNF_GO|id=GO:0030183 |text = B cell differentiation}} {{GNF_GO|id=GO:0030217 |text = T cell differentiation}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 53335
    | Hs_Ensembl = ENSG00000119866
    | Hs_RefseqProtein = NP_060484
    | Hs_RefseqmRNA = NM_018014
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 2
    | Hs_GenLoc_start = 60531806
    | Hs_GenLoc_end = 60634121
    | Hs_Uniprot = Q9H165
    | Mm_EntrezGene = 14025
    | Mm_Ensembl = ENSMUSG00000000861
    | Mm_RefseqmRNA = NM_016707
    | Mm_RefseqProtein = NP_057916
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 11
    | Mm_GenLoc_start = 23978117
    | Mm_GenLoc_end = 24073194
    | Mm_Uniprot = Q3US10
  }}
}}
'''B-cell CLL/lymphoma 11A (zinc finger protein)''', also known as '''BCL11A''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: BCL11A B-cell CLL/lymphoma 11A (zinc finger protein)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=53335| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
The ''BCL11A'' gene encodes for a regulatory C2H2 type zinc-finger protein, that can bind to the DNA. Five alternatively spliced transcript variants of this gene, which encode distinct isoforms, have been reported.<ref name="entrez"/> The protein associates with the [[SWI/SNF|SWI/SNF complex]], that regulates gene expression via chromatin remodelling.<ref>{{cite journal | vauthors = Kadoch C, Hargreaves DC, Hodges C, Elias L, Ho L, Ranish J, Crabtree GR | title = Proteomic and bioinformatic analysis of mammalian SWI/SNF complexes identifies extensive roles in human malignancy | journal = Nature Genetics | volume = 45 | issue = 6 | pages = 592–601 | date = June 2013 | pmid = 23644491 | pmc = 3667980 | doi = 10.1038/ng.2628 }}</ref>
{{PBB_Summary
| section_title =
| summary_text = This gene encodes a C2H2 type zinc-finger protein by its similarity to the mouse Bcl11a/Evi9 protein. The corresponding mouse gene is a common site of [[retroviral integration]] in myeloid leukemia, and may function as a leukemia disease gene, in part, through its interaction with BCL6. During hematopoietic cell differentiation, this gene is down-regulated. It is possibly involved in lymphoma pathogenesis since translocations associated with B-cell malignancies also deregulates its expression. Five alternatively spliced transcript variants of this gene, which encode distinct isoforms, have been reported.<ref name="entrez">{{cite web | title = Entrez Gene: BCL11A B-cell CLL/lymphoma 11A (zinc finger protein)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=53335| accessdate = }}</ref>
}}


==References==
''BCL11A'' is highly expressed in several hematopoietic lineages, and plays a role in the switch from [[Globin|γ- to β-globin]] expression during the fetal to adult [[erythropoiesis]] transition.<ref>{{cite journal | vauthors = Smith EC, Luc S, Croney DM, Woodworth MB, Greig LC, Fujiwara Y, Nguyen M, Sher F, Macklis JD, Bauer DE, Orkin SH | title = Bcl11a erythroid enhancer | journal = Blood | volume = 128 | issue = 19 | pages = 2338–2342 | date = November 2016 | pmid = 27707736 | pmc = 5106112 | doi = 10.1182/blood-2016-08-736249 }}</ref>
{{reflist|2}}
 
==Further reading==
Furthermore, BCL11A is expressed in the brain, where it forms a protein complex with CASK to regulate axon outgrowth and branching.<ref name=":0">{{cite journal | vauthors = Kuo TY, Hong CJ, Chien HL, Hsueh YP | title = X-linked mental retardation gene CASK interacts with Bcl11A/CTIP1 and regulates axon branching and outgrowth | language = de | journal = Journal of Neuroscience Research | volume = 88 | issue = 11 | pages = 2364–73 | date = August 2010 | pmid = 20623620 | doi = 10.1002/jnr.22407 }}</ref> In the [[neocortex]], BCL11A binds to the ''TBR1'' regulatory region and inhibits the expression of ''TBR1''.<ref>{{cite journal | vauthors = Cánovas J, Berndt FA, Sepúlveda H, Aguilar R, Veloso FA, Montecino M, Oliva C, Maass JC, Sierralta J, Kukuljan M | title = The Specification of Cortical Subcerebral Projection Neurons Depends on the Direct Repression of TBR1 by CTIP1/BCL11a | journal = The Journal of Neuroscience | volume = 35 | issue = 19 | pages = 7552–64 | date = May 2015 | pmid = 25972180 | doi = 10.1523/JNEUROSCI.0169-15.2015 }}</ref>
 
== Clinical significance ==
The corresponding ''Bcl11a'' mouse gene is a common site of [[retroviral integration]] in [[myeloid leukemia]], and may function as a leukemia disease gene, in part, through its interaction with BCL6. During hematopoietic cell differentiation, this gene is down-regulated. It is possibly involved in lymphoma pathogenesis since translocations associated with B-cell malignancies also deregulates its expression. In addition, BCL11A has been found to play a role in the suppression of fetal hemoglobin production. Therapeutic strategies aimed at increasing fetal globin production in diseases such as [[beta thalassemia]] and [[Sickle cell disease|sickle cell anemia]] by inhibiting BCL11A are currently being explored.
 
Furthermore, heterozygous ''de novo'' mutations in ''BCL11A'' have been identified in an [[Intellectual disability|intellectual disability disorder]], accompanied with global developmental delay and [[Autism spectrum|autism spectrum disorder]].<ref name=":1">{{cite journal | vauthors = Dias C, Estruch SB, Graham SA, McRae J, Sawiak SJ, Hurst JA, Joss SK, Holder SE, Morton JE, Turner C, Thevenon J, Mellul K, Sánchez-Andrade G, Ibarra-Soria X, Deriziotis P, Santos RF, Lee SC, Faivre L, Kleefstra T, Liu P, Hurles ME, Fisher SE, Logan DW | title = BCL11A Haploinsufficiency Causes an Intellectual Disability Syndrome and Dysregulates Transcription | journal = American Journal of Human Genetics | volume = 99 | issue = 2 | pages = 253–74 | date = August 2016 | pmid = 27453576 | pmc = 4974071 | doi = 10.1016/j.ajhg.2016.05.030 }}</ref> These mutations disrupt BCL11A homodimerization and transcriptional regulation.
 
== Interactions ==
 
BCL11A has been shown to interact with a number of proteins. BCL11A was initially discovered as a [[COUP-TFI]] interacting protein.<ref>{{cite journal | vauthors = Avram D, Fields A, Senawong T, Topark-Ngarm A, Leid M | title = COUP-TF (chicken ovalbumin upstream promoter transcription factor)-interacting protein 1 (CTIP1) is a sequence-specific DNA binding protein | journal = The Biochemical Journal | volume = 368 | issue = Pt 2 | pages = 555–63 | date = December 2002 | pmid = 12196208 | pmc = 1223006 | doi = 10.1042/bj20020496 }}</ref> In the nucleus, BCL11A forms paraspeckles that co-localize with [[NONO (protein)|NONO]].<ref name=":1" /> In neurons, BCL11A interacts with [[CASK]] to regulate target genes.<ref name=":0" /> Furthermore, BCL11A interacts with the neuron-specific protein [[TBR1]], which is also implicated in intellectual disability and autism spectrum disorder.<ref>{{cite journal | vauthors = den Hoed J, Sollis E, Venselaar H, Estruch SB, Deriziotis P, Fisher SE | title = Functional characterization of TBR1 variants in neurodevelopmental disorder | journal = Scientific Reports | volume = 8 | issue = 1 | pages = 14279 | date = September 2018 | pmid = 30250039 | pmc = 6155134 | doi = 10.1038/s41598-018-32053-6 }}</ref>
 
== References ==
{{reflist}}
 
== Further reading ==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_Further_reading
* {{cite journal | vauthors = | title = Toward a complete human genome sequence | journal = Genome Research | volume = 8 | issue = 11 | pages = 1097–108 | date = November 1998 | pmid = 9847074 | doi = 10.1101/gr.8.11.1097 }}
| citations =
* {{cite journal | vauthors = Avram D, Fields A, Pretty On Top K, Nevrivy DJ, Ishmael JE, Leid M | title = 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 | journal = The Journal of Biological Chemistry | volume = 275 | issue = 14 | pages = 10315–22 | date = April 2000 | pmid = 10744719 | pmc = 2819356 | doi = 10.1074/jbc.275.14.10315 }}
*{{cite journal | author= |title=Toward a complete human genome sequence. |journal=Genome Res. |volume=8 |issue= 11 |pages= 1097-108 |year= 1999 |pmid= 9847074 |doi= }}
* {{cite journal | vauthors = Nakamura T, Yamazaki Y, Saiki Y, Moriyama M, Largaespada DA, Jenkins NA, Copeland NG | title = Evi9 encodes a novel zinc finger protein that physically interacts with BCL6, a known human B-cell proto-oncogene product | journal = Molecular and Cellular Biology | volume = 20 | issue = 9 | pages = 3178–86 | date = May 2000 | pmid = 10757802 | pmc = 85612 | doi = 10.1128/MCB.20.9.3178-3186.2000 }}
*{{cite journal | author=Avram D, Fields A, Pretty On Top K, ''et al.'' |title=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. |journal=J. Biol. Chem. |volume=275 |issue= 14 |pages= 10315-22 |year= 2000 |pmid= 10744719 |doi= }}
* {{cite journal | vauthors = Saiki Y, Yamazaki Y, Yoshida M, Katoh O, Nakamura T | title = Human EVI9, a homologue of the mouse myeloid leukemia gene, is expressed in the hematopoietic progenitors and down-regulated during myeloid differentiation of HL60 cells | journal = Genomics | volume = 70 | issue = 3 | pages = 387–91 | date = December 2000 | pmid = 11161790 | doi = 10.1006/geno.2000.6385 }}
*{{cite journal | author=Nakamura T, Yamazaki Y, Saiki Y, ''et al.'' |title=Evi9 encodes a novel zinc finger protein that physically interacts with BCL6, a known human B-cell proto-oncogene product. |journal=Mol. Cell. Biol. |volume=20 |issue= 9 |pages= 3178-86 |year= 2000 |pmid= 10757802 |doi= }}
* {{cite journal | vauthors = Nagase T, Nakayama M, Nakajima D, Kikuno R, Ohara O | title = Prediction of the coding sequences of unidentified human genes. XX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro | journal = DNA Research | volume = 8 | issue = 2 | pages = 85–95 | date = April 2001 | pmid = 11347906 | doi = 10.1093/dnares/8.2.85 }}
*{{cite journal | author=Saiki Y, Yamazaki Y, Yoshida M, ''et al.'' |title=Human EVI9, a homologue of the mouse myeloid leukemia gene, is expressed in the hematopoietic progenitors and down-regulated during myeloid differentiation of HL60 cells. |journal=Genomics |volume=70 |issue= 3 |pages= 387-91 |year= 2001 |pmid= 11161790 |doi= 10.1006/geno.2000.6385 }}
* {{cite journal | vauthors = Martín-Subero JI, Gesk S, Harder L, Sonoki T, Tucker PW, Schlegelberger B, Grote W, Novo FJ, Calasanz MJ, Hansmann ML, Dyer MJ, Siebert R | title = Recurrent involvement of the REL and BCL11A loci in classical Hodgkin lymphoma | journal = Blood | volume = 99 | issue = 4 | pages = 1474–7 | date = February 2002 | pmid = 11830502 | doi = 10.1182/blood.V99.4.1474 }}
*{{cite journal | author=Nagase T, Nakayama M, Nakajima D, ''et al.'' |title=Prediction of the coding sequences of unidentified human genes. XX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. |journal=DNA Res. |volume=8 |issue= 2 |pages= 85-95 |year= 2001 |pmid= 11347906 |doi= }}
* {{cite journal | vauthors = Küppers R, Sonoki T, Satterwhite E, Gesk S, Harder L, Oscier DG, Tucker PW, Dyer MJ, Siebert R | title = Lack of somatic hypermutation of IG V(H) genes in lymphoid malignancies with t(2;14)(p13;q32) translocation involving the BCL11A gene | journal = Leukemia | volume = 16 | issue = 5 | pages = 937–9 | date = May 2002 | pmid = 11986957 | doi = 10.1038/sj.leu.2402480 }}
*{{cite journal  | author=Satterwhite E, Sonoki T, Willis TG, ''et al.'' |title=The BCL11 gene family: involvement of BCL11A in lymphoid malignancies. |journal=Blood |volume=98 |issue= 12 |pages= 3413-20 |year= 2001 |pmid= 11719382 |doi=  }}
* {{cite journal | vauthors = Senawong T, Peterson VJ, Leid M | title = BCL11A-dependent recruitment of SIRT1 to a promoter template in mammalian cells results in histone deacetylation and transcriptional repression | journal = Archives of Biochemistry and Biophysics | volume = 434 | issue = 2 | pages = 316–25 | date = February 2005 | pmid = 15639232 | pmc = 2819353 | doi = 10.1016/j.abb.2004.10.028 }}
*{{cite journal | author=Martín-Subero JI, Gesk S, Harder L, ''et al.'' |title=Recurrent involvement of the REL and BCL11A loci in classical Hodgkin lymphoma. |journal=Blood |volume=99 |issue= 4 |pages= 1474-7 |year= 2002 |pmid= 11830502 |doi= }}
* {{cite journal | vauthors = Liu H, Ippolito GC, Wall JK, Niu T, Probst L, Lee BS, Pulford K, Banham AH, Stockwin L, Shaffer AL, Staudt LM, Das C, Dyer MJ, Tucker PW | title = Functional studies of BCL11A: characterization of the conserved BCL11A-XL splice variant and its interaction with BCL6 in nuclear paraspeckles of germinal center B cells | journal = Molecular Cancer | volume = 5 | issue =  | pages = 18 | date = May 2006 | pmid = 16704730 | pmc = 1526750 | doi = 10.1186/1476-4598-5-18 }}
*{{cite journal | author=Küppers R, Sonoki T, Satterwhite E, ''et al.'' |title=Lack of somatic hypermutation of IG V(H) genes in lymphoid malignancies with t(2;14)(p13;q32) translocation involving the BCL11A gene. |journal=Leukemia |volume=16 |issue= 5 |pages= 937-9 |year= 2002 |pmid= 11986957 |doi= 10.1038/sj.leu.2402480 }}
* {{cite journal | vauthors = Weniger MA, Pulford K, Gesk S, Ehrlich S, Banham AH, Lyne L, Martin-Subero JI, Siebert R, Dyer MJ, Möller P, Barth TF | title = Gains of the proto-oncogene BCL11A and nuclear accumulation of BCL11A(XL) protein are frequent in primary mediastinal B-cell lymphoma | journal = Leukemia | volume = 20 | issue = 10 | pages = 1880–2 | date = October 2006 | pmid = 16871282 | doi = 10.1038/sj.leu.2404324 }}
*{{cite journal | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
* {{cite journal | vauthors = Szafranski K, Schindler S, Taudien S, Hiller M, Huse K, Jahn N, Schreiber S, Backofen R, Platzer M | title = Violating the splicing rules: TG dinucleotides function as alternative 3' splice sites in U2-dependent introns | journal = Genome Biology | volume = 8 | issue = 8 | pages = R154 | year = 2007 | pmid = 17672918 | pmc = 2374985 | doi = 10.1186/gb-2007-8-8-r154 }}
*{{cite journal  | author=Ota T, Suzuki Y, Nishikawa T, ''et al.'' |title=Complete sequencing and characterization of 21,243 full-length human cDNAs. |journal=Nat. Genet. |volume=36 |issue= 1 |pages= 40-5 |year= 2004 |pmid= 14702039 |doi= 10.1038/ng1285 }}
*{{cite journal  | author=Gerhard DS, Wagner L, Feingold EA, ''et al.'' |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121-7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 }}
*{{cite journal  | author=Senawong T, Peterson VJ, Leid M |title=BCL11A-dependent recruitment of SIRT1 to a promoter template in mammalian cells results in histone deacetylation and transcriptional repression. |journal=Arch. Biochem. Biophys. |volume=434 |issue= 2 |pages= 316-25 |year= 2005 |pmid= 15639232 |doi= 10.1016/j.abb.2004.10.028 }}
*{{cite journal | author=Liu H, Ippolito GC, Wall JK, ''et al.'' |title=Functional studies of BCL11A: characterization of the conserved BCL11A-XL splice variant and its interaction with BCL6 in nuclear paraspeckles of germinal center B cells. |journal=Mol. Cancer |volume=5 |issue=  |pages= 18 |year= 2006 |pmid= 16704730 |doi= 10.1186/1476-4598-5-18 }}
*{{cite journal | author=Weniger MA, Pulford K, Gesk S, ''et al.'' |title=Gains of the proto-oncogene BCL11A and nuclear accumulation of BCL11A(XL) protein are frequent in primary mediastinal B-cell lymphoma. |journal=Leukemia |volume=20 |issue= 10 |pages= 1880-2 |year= 2006 |pmid= 16871282 |doi= 10.1038/sj.leu.2404324 }}
*{{cite journal | author=Szafranski K, Schindler S, Taudien S, ''et al.'' |title=Violating the splicing rules: TG dinucleotides function as alternative 3' splice sites in U2-dependent introns. |journal= |volume=8 |issue= 8 |pages= R154 |year= |pmid= 17672918 |doi= 10.1186/gb-2007-8-8-r154 }}
}}
{{refend}}
{{refend}}


== External links ==
== External links ==
* {{MeshName|BCL11A+protein,+human}}
* {{MeshName|BCL11A+protein,+human}}
* {{FactorBook|BCL11A}}
* {{UCSC gene info|BCL11A}}


{{NLM content}}
{{Transcription factors|g2}}


{{protein-stub}}
{{NLM content}}
{{Transcription factors}}
[[Category:Transcription factors]]
[[Category:Transcription factors]]
{{WikiDoc Sources}}
 
{{gene-2-stub}}

Latest revision as of 06:22, 2 October 2018

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

B-cell lymphoma/leukemia 11A is a protein that in humans is encoded by the BCL11A gene.[1][2][3]

Function

The BCL11A gene encodes for a regulatory C2H2 type zinc-finger protein, that can bind to the DNA. Five alternatively spliced transcript variants of this gene, which encode distinct isoforms, have been reported.[3] The protein associates with the SWI/SNF complex, that regulates gene expression via chromatin remodelling.[4]

BCL11A is highly expressed in several hematopoietic lineages, and plays a role in the switch from γ- to β-globin expression during the fetal to adult erythropoiesis transition.[5]

Furthermore, BCL11A is expressed in the brain, where it forms a protein complex with CASK to regulate axon outgrowth and branching.[6] In the neocortex, BCL11A binds to the TBR1 regulatory region and inhibits the expression of TBR1.[7]

Clinical significance

The corresponding Bcl11a mouse gene is a common site of retroviral integration in myeloid leukemia, and may function as a leukemia disease gene, in part, through its interaction with BCL6. During hematopoietic cell differentiation, this gene is down-regulated. It is possibly involved in lymphoma pathogenesis since translocations associated with B-cell malignancies also deregulates its expression. In addition, BCL11A has been found to play a role in the suppression of fetal hemoglobin production. Therapeutic strategies aimed at increasing fetal globin production in diseases such as beta thalassemia and sickle cell anemia by inhibiting BCL11A are currently being explored.

Furthermore, heterozygous de novo mutations in BCL11A have been identified in an intellectual disability disorder, accompanied with global developmental delay and autism spectrum disorder.[8] These mutations disrupt BCL11A homodimerization and transcriptional regulation.

Interactions

BCL11A has been shown to interact with a number of proteins. BCL11A was initially discovered as a COUP-TFI interacting protein.[9] In the nucleus, BCL11A forms paraspeckles that co-localize with NONO.[8] In neurons, BCL11A interacts with CASK to regulate target genes.[6] Furthermore, BCL11A interacts with the neuron-specific protein TBR1, which is also implicated in intellectual disability and autism spectrum disorder.[10]

References

  1. ↑ Satterwhite E, Sonoki T, Willis TG, Harder L, Nowak R, Arriola EL, Liu H, Price HP, Gesk S, Steinemann D, Schlegelberger B, Oscier DG, Siebert R, Tucker PW, Dyer MJ (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.
  2. ↑ Uda M, Galanello R, Sanna S, Lettre G, Sankaran VG, Chen W, et al. (February 2008). "Genome-wide association study shows BCL11A associated with persistent fetal hemoglobin and amelioration of the phenotype of beta-thalassemia". Proceedings of the National Academy of Sciences of the United States of America. 105 (5): 1620–5. doi:10.1073/pnas.0711566105. PMC 2234194. PMID 18245381.
  3. ↑ 3.0 3.1 "Entrez Gene: BCL11A B-cell CLL/lymphoma 11A (zinc finger protein)".
  4. ↑ Kadoch C, Hargreaves DC, Hodges C, Elias L, Ho L, Ranish J, Crabtree GR (June 2013). "Proteomic and bioinformatic analysis of mammalian SWI/SNF complexes identifies extensive roles in human malignancy". Nature Genetics. 45 (6): 592–601. doi:10.1038/ng.2628. PMC 3667980. PMID 23644491.
  5. ↑ Smith EC, Luc S, Croney DM, Woodworth MB, Greig LC, Fujiwara Y, Nguyen M, Sher F, Macklis JD, Bauer DE, Orkin SH (November 2016). "Bcl11a erythroid enhancer". Blood. 128 (19): 2338–2342. doi:10.1182/blood-2016-08-736249. PMC 5106112. PMID 27707736.
  6. ↑ 6.0 6.1 Kuo TY, Hong CJ, Chien HL, Hsueh YP (August 2010). "X-linked mental retardation gene CASK interacts with Bcl11A/CTIP1 and regulates axon branching and outgrowth". Journal of Neuroscience Research (in Deutsch). 88 (11): 2364–73. doi:10.1002/jnr.22407. PMID 20623620.
  7. ↑ Cánovas J, Berndt FA, Sepúlveda H, Aguilar R, Veloso FA, Montecino M, Oliva C, Maass JC, Sierralta J, Kukuljan M (May 2015). "The Specification of Cortical Subcerebral Projection Neurons Depends on the Direct Repression of TBR1 by CTIP1/BCL11a". The Journal of Neuroscience. 35 (19): 7552–64. doi:10.1523/JNEUROSCI.0169-15.2015. PMID 25972180.
  8. ↑ 8.0 8.1 Dias C, Estruch SB, Graham SA, McRae J, Sawiak SJ, Hurst JA, Joss SK, Holder SE, Morton JE, Turner C, Thevenon J, Mellul K, Sánchez-Andrade G, Ibarra-Soria X, Deriziotis P, Santos RF, Lee SC, Faivre L, Kleefstra T, Liu P, Hurles ME, Fisher SE, Logan DW (August 2016). "BCL11A Haploinsufficiency Causes an Intellectual Disability Syndrome and Dysregulates Transcription". American Journal of Human Genetics. 99 (2): 253–74. doi:10.1016/j.ajhg.2016.05.030. PMC 4974071. PMID 27453576.
  9. ↑ Avram D, Fields A, Senawong T, Topark-Ngarm A, Leid M (December 2002). "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. doi:10.1042/bj20020496. PMC 1223006. PMID 12196208.
  10. ↑ den Hoed J, Sollis E, Venselaar H, Estruch SB, Deriziotis P, Fisher SE (September 2018). "Functional characterization of TBR1 variants in neurodevelopmental disorder". Scientific Reports. 8 (1): 14279. doi:10.1038/s41598-018-32053-6. PMC 6155134. PMID 30250039.

Further reading

External links

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