BCL-6 corepressor explained

BCL-6 corepressor is a protein that in humans is encoded by the BCOR gene.^{[1] [2]}

Function

The protein encoded by this gene was identified as an interacting corepressor of BCL6, a POZ/zinc finger transcription repressor that is required for germinal center formation and may influence apoptosis. This protein selectively interacts with the POZ domain of BCL6, but not with eight other POZ proteins. Specific class I and II histone deacetylases (HDACs) have been shown to interact with this protein, which suggests a possible link between the two classes of HDACs. At least four alternatively spliced transcript variants, which encode different isoforms, have been reported for this gene.^[2]

Clinical significance

Mutations in the BCOR gene cause a form of syndromic microphthalmia (small eye) called MCOPS2. This syndrome incorporates microphthalmia, congenital cataracts, cardiac defects, dental defects and skeletal anomalies. Mutations in this gene have also been found associated to acute myeloid leukemia.^[3]

Interactions

BCOR has been shown to interact with MLLT3^[4] and BCL6.^[1]

Further reading

• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . Jan 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . Oct 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Nagase T, Kikuno R, Nakayama M, Hirosawa M, Ohara O . Prediction of the coding sequences of unidentified human genes. XVIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro . DNA Research . 7 . 4 . 273–81 . Aug 2000 . 10997877 . 10.1093/dnares/7.4.271 . free .
• Tang TT, Dowbenko D, Jackson A, Toney L, Lewin DA, Dent AL, Lasky LA . The forkhead transcription factor AFX activates apoptosis by induction of the BCL-6 transcriptional repressor . The Journal of Biological Chemistry . 277 . 16 . 14255–65 . Apr 2002 . 11777915 . 10.1074/jbc.M110901200 . free .
• Ng D, Hadley DW, Tifft CJ, Biesecker LG . Genetic heterogeneity of syndromic X-linked recessive microphthalmia-anophthalmia: is Lenz microphthalmia a single disorder? . American Journal of Medical Genetics . 110 . 4 . 308–14 . Jul 2002 . 12116202 . 10.1002/ajmg.10484 .
• Tomsig JL, Snyder SL, Creutz CE . Identification of targets for calcium signaling through the copine family of proteins. Characterization of a coiled-coil copine-binding motif . The Journal of Biological Chemistry . 278 . 12 . 10048–54 . Mar 2003 . 12522145 . 10.1074/jbc.M212632200 . free .
• Srinivasan RS, de Erkenez AC, Hemenway CS . The mixed lineage leukemia fusion partner AF9 binds specific isoforms of the BCL-6 corepressor . Oncogene . 22 . 22 . 3395–406 . May 2003 . 12776190 . 10.1038/sj.onc.1206361 . 34517481 .
• Ng D, Thakker N, Corcoran CM, Donnai D, Perveen R, Schneider A, Hadley DW, Tifft C, Zhang L, Wilkie AO, van der Smagt JJ, Gorlin RJ, Burgess SM, Bardwell VJ, Black GC, Biesecker LG . Oculofaciocardiodental and Lenz microphthalmia syndromes result from distinct classes of mutations in BCOR . Nature Genetics . 36 . 4 . 411–6 . Apr 2004 . 15004558 . 10.1038/ng1321 . free .
• Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, Cohn MA, Cantley LC, Gygi SP . Large-scale characterization of HeLa cell nuclear phosphoproteins . Proceedings of the National Academy of Sciences of the United States of America . 101 . 33 . 12130–5 . Aug 2004 . 15302935 . 514446 . 10.1073/pnas.0404720101 . 2004PNAS..10112130B . free .
• Horn D, Chyrek M, Kleier S, Lüttgen S, Bolz H, Hinkel GK, Korenke GC, Riess A, Schell-Apacik C, Tinschert S, Wieczorek D, Gillessen-Kaesbach G, Kutsche K . Novel mutations in BCOR in three patients with oculo-facio-cardio-dental syndrome, but none in Lenz microphthalmia syndrome . European Journal of Human Genetics . 13 . 5 . 563–9 . May 2005 . 15770227 . 10.1038/sj.ejhg.5201391 . free .
• Lee JA, Suh DC, Kang JE, Kim MH, Park H, Lee MN, Kim JM, Jeon BN, Roh HE, Yu MY, Choi KY, Kim KY, Hur MW . Transcriptional activity of Sp1 is regulated by molecular interactions between the zinc finger DNA binding domain and the inhibitory domain with corepressors, and this interaction is modulated by MEK . The Journal of Biological Chemistry . 280 . 30 . 28061–71 . Jul 2005 . 15878880 . 10.1074/jbc.M414134200 . free .
• Lim J, Hao T, Shaw C, Patel AJ, Szabó G, Rual JF, Fisk CJ, Li N, Smolyar A, Hill DE, Barabási AL, Vidal M, Zoghbi HY . A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration . Cell . 125 . 4 . 801–14 . May 2006 . 16713569 . 10.1016/j.cell.2006.03.032 . 13709685 . free .
• Gearhart MD, Corcoran CM, Wamstad JA, Bardwell VJ . Polycomb group and SCF ubiquitin ligases are found in a novel BCOR complex that is recruited to BCL6 targets . Molecular and Cellular Biology . 26 . 18 . 6880–9 . Sep 2006 . 16943429 . 1592854 . 10.1128/MCB.00630-06 .
• Hilton EN, Manson FD, Urquhart JE, Johnston JJ, Slavotinek AM, Hedera P, Stattin EL, Nordgren A, Biesecker LG, Black GC . Left-sided embryonic expression of the BCL-6 corepressor, BCOR, is required for vertebrate laterality determination . Human Molecular Genetics . 16 . 14 . 1773–82 . Jul 2007 . 17517692 . 10.1093/hmg/ddm125 . free .

External links

• GeneReviews/NCBI/NIH/UW entry on Anophthalmia / Microphthalmia Overview
• GeneReviews/NCBI/NIH/UW entry on Lenz Microphthalmia Syndrome

Notes and References

1. Huynh KD, Fischle W, Verdin E, Bardwell VJ . BCoR, a novel corepressor involved in BCL-6 repression . Genes & Development . 14 . 14 . 1810–23 . Jul 2000 . 10898795 . 316791 . 10.1101/gad.14.14.1810 .
2. Web site: Entrez Gene: BCOR BCL6 co-repressor.
3. Grossmann V, Tiacci E, Holmes AB, Kohlmann A, Martelli MP, Kern W, Spanhol-Rosseto A, Klein HU, Dugas M, Schindela S, Trifonov V, Schnittger S, Haferlach C, Bassan R, Wells VA, Spinelli O, Chan J, Rossi R, Baldoni S, De Carolis L, Goetze K, Serve H, Peceny R, Kreuzer KA, Oruzio D, Specchia G, Di Raimondo F, Fabbiano F, Sborgia M, Liso A, Farinelli L, Rambaldi A, Pasqualucci L, Rabadan R, Haferlach T, Falini B . Whole-exome sequencing identifies somatic mutations of BCOR in acute myeloid leukemia with normal karyotype . Blood . 118 . 23 . 6153–63 . Dec 2011 . 22012066 . 10.1182/blood-2011-07-365320 . free .
4. Srinivasan RS, de Erkenez AC, Hemenway CS . The mixed lineage leukemia fusion partner AF9 binds specific isoforms of the BCL-6 corepressor . Oncogene . 22 . 22 . 3395–406 . May 2003 . 12776190 . 10.1038/sj.onc.1206361 . 34517481 .