BCoR, a novel corepressor involved in BCL-6 repression.
BCoR, a novel corepressor involved in BCL-6 repression.
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DOI：
10.1101/gad.14.14.1810
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发表时间：
2000-07
影响因子：
10.5
通讯作者：
K. Huynh;W. Fischle;E. Verdin;V. Bardwell
中科院分区：
文献类型：
--
作者：
K. Huynh;W. Fischle;E. Verdin;V. Bardwell
BCL-6编码一个POZ/锌指转录抑制因子，它是生发中心形成所必需的，并可能影响凋亡。染色体易位导致的BCL-6异常表达与某些亚型的非霍奇金淋巴瘤有关。BCL-6和其他几种POZ蛋白的POZ结构域与辅阻遏物N-CoR和SMRT相互作用。在这里，我们确定和表征一种新的辅阻遏物BCoR（BCL-6相互作用辅阻遏物），这是在人体组织中普遍表达。BCoR在与DNA连接时可以作为辅阻遏物发挥作用，并且在过表达时可以增强BCL-6的阻遏作用。特定的I类和II类组蛋白脱乙酰酶（HDAC）在体内与BCoR相互作用，表明BCoR可能在功能上连接这两类HDAC。引人注目的是，BCoR选择性地与BCL-6的POZ结构域相互作用，但不与其他八种测试的POZ蛋白（包括PLZF）相互作用。此外，BCL-6 POZ结构域与SMRT、N-CoR和BCoR之间的相互作用是相互排斥的。BCL-6/BCoR相互作用的特异性表明BCoR可能在BCL-6相关淋巴瘤中起作用。
BCL-6 encodes a POZ/zinc finger transcriptional repressor that is required for germinal center formation and may influence apoptosis. Aberrant expression of BCL-6 due to chromosomal translocations is implicated in certain subtypes of non-Hodgkin's lymphoma. The POZ domains of BCL-6 and several other POZ proteins interact with corepressors N-CoR and SMRT. Here we identify and characterize a novel corepressor BCoR (BCL-6 interacting corepressor), which is expressed ubiquitously in human tissues. BCoR can function as a corepressor when tethered to DNA and, when overexpressed, can potentiate BCL-6 repression. Specific class I and II histone deacetylases (HDACs) interact in vivo with BCoR, suggesting that BCoR may functionally link these two classes of HDACs. Strikingly, BCoR interacts selectively with the POZ domain of BCL-6 but not with eight other POZ proteins tested, including PLZF. Additionally, interactions between the BCL-6 POZ domain and SMRT, N-CoR, and BCoR are mutually exclusive. The specificity of the BCL-6/BCoR interaction suggests that BCoR may have a role in BCL-6-associated lymphomas.