Functional analysis of a novel family of inhibitor of differentiation

我们最近发现e1a样分化抑制剂-1 （EID-1）是一种prb结合蛋白。EID-1通过阻断p300的组蛋白乙酰转移酶（HAT）活性来抑制分化，p300是一种促进分化的转录辅激活因子。除p300外，EID-1与核心组蛋白结合，这种结合抑制组蛋白乙酰化（组蛋白掩蔽）。pRB与EID-1结合后促进分化，并帮助EID-1降解。我们还鉴定出EID-2和EID-3是EID-1的家族蛋白。当在细胞中过表达时，EID-2和-3与ED-1一样抑制分化。令人惊讶的是，EID-1并没有阻断p300的HAT活性，而是与组蛋白去乙酰化酶（HDAC）结合。EID-2也与Smads相互作用并抑制转录。这些结果表明，EIDs属于一个新的蛋白家族，其功能是参与分化的转录抑制因子。我们现在正在培育具有EID家族基因的敲除小鼠，并研究它们与人类疾病的关系。

We recently identified E1A-like inhibitor of differentiation-1 (EID-1) as a pRB-binding protein. EID-1 inhibited differentiation via blocking histone acetyltransferase (HAT) activity of p300, a transcriptional coactivator which promotes differentiation. In addition to p300, EID-1 bound to core histones and this binding inhibited histone acetylation (histone masking). pRB promoted differentiation when it bound and helped degradation of EID-1.We also identified EID-2 and EID-3 as family proteins of EID-1. When overexpressed in the cells, EID-2 and -3 inhibited differentiation like ED-1. Surprisingly, EID-1 did not block HAT activity of p300 rather it bound to histone deacetylases (HDAC). EID-2 also interacted with Smads and inhibited transcription.These results shows that EIDs belong to a new protein family which functions as repressors of transcription involved in differentiation. We are now generating knock out mice of EID family genes and investigating their involvement to human diseases.