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SUMOylated SoxE 因子招募 Grg4 并作为转录抑制剂在神经嵴中发挥作用。

SUMOylated SoxE factors recruit Grg4 and function as transcriptional repressors in the neural crest.

机构信息

Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208, USA.

出版信息

J Cell Biol. 2012 Sep 3;198(5):799-813. doi: 10.1083/jcb.201204161. Epub 2012 Aug 27.

Abstract

A growing number of transcriptional regulatory proteins are known to be modified by the small ubiquitin-like protein, SUMO. Posttranslational modification by SUMO may be one means by which transcriptional regulatory factors that play context-dependent roles in multiple processes can be regulated such that they direct the appropriate cellular and developmental outcomes. In early vertebrate embryos, SUMOylation of SoxE transcription factors profoundly affects their function, inhibiting their neural crest-inducing activity and promoting ear formation. In this paper, we provide mechanistic insight into how SUMO modification modulates SoxE function. We show that SUMOylation dramatically altered recruitment of transcriptional coregulator factors by SoxE proteins, displacing coactivators CREB-binding protein/p300 while promoting the recruitment of a corepressor, Grg4. These data demonstrate that SoxE proteins can function as transcriptional repressors in a SUMO-dependent manner. They further suggest a novel multivalent mechanism for SUMO-mediated recruitment of transcriptional coregulatory factors.

摘要

越来越多的转录调控蛋白被发现可以被小分子泛素样蛋白 SUMO 修饰。SUMO 的翻译后修饰可能是一种调节转录调控因子的方式,这些因子在多种过程中发挥着依赖于背景的作用,从而可以指导适当的细胞和发育结果。在早期的脊椎动物胚胎中,SoxE 转录因子的 SUMO 化极大地影响了它们的功能,抑制了它们的神经嵴诱导活性,并促进了耳朵的形成。在本文中,我们提供了关于 SUMO 修饰如何调节 SoxE 功能的机制见解。我们表明,SUMO 化极大地改变了 SoxE 蛋白募集转录共激活因子的情况,取代了共激活因子 CREB 结合蛋白/p300,同时促进了核心抑制因子 Grg4 的募集。这些数据表明 SoxE 蛋白可以依赖 SUMO 作为转录抑制因子发挥作用。它们进一步表明了一种新的 SUMO 介导的转录共调节因子募集的多价机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acd9/3432773/af5f623cd365/JCB_201204161_Fig1.jpg

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