Youn H D, Liu J O
Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA.
Immunity. 2000 Jul;13(1):85-94. doi: 10.1016/s1074-7613(00)00010-8.
TCR signaling leading to thymocyte apoptosis is mediated through the expression of the Nur77 family of orphan nuclear receptors. MEF2 has been shown to be the major transcription factor responsible for calcium-dependent Nur77 transcription. Cabin1 was recently identified as a transcriptional repressor of MEF2, which can be released from MEF2 in a calcium-dependent fashion. The molecular basis of repression of MEF2 by Cabin1, however, has remained unknown. We report that Cabin1 represses MEF2 by two distinct mechanisms. Cabin1 recruits mSin3 and its associated histone deacetylases 1 and 2; Cabin1 also competes with p300 for binding to MEF2. Thus, activation of MEF2 and the consequent transcription of Nur77 are controlled by the association of MEF2 with the histone deacetylases via the calcium-dependent repressor Cabin1.
导致胸腺细胞凋亡的TCR信号传导是通过孤儿核受体Nur77家族的表达介导的。MEF2已被证明是负责钙依赖性Nur77转录的主要转录因子。Cabin1最近被鉴定为MEF2的转录抑制因子，它可以以钙依赖性方式从MEF2中释放出来。然而，Cabin1对MEF2的抑制作用的分子基础仍然未知。我们报告称，Cabin1通过两种不同的机制抑制MEF2。Cabin1招募mSin3及其相关的组蛋白去乙酰化酶1和2；Cabin1还与p300竞争与MEF2的结合。因此，MEF2的激活以及随后Nur77的转录是由MEF2通过钙依赖性抑制因子Cabin1与组蛋白去乙酰化酶的结合来控制的。
