Functional analysis of a novel family of inhibitor of differentiation

点击翻译按钮获取中文摘要

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.