Reversible acetylation of Lin28 mediated by PCAF and SIRT1
Reversible acetylation of Lin28 mediated by PCAF and SIRT1
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PCAF 和 SIRT1 介导的 Lin28 可逆乙酰化
DOI：
10.1016/j.bbamcr.2014.03.001
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发表时间：
2014-06-01
影响因子：
5.1
通讯作者：
Shen, Yu-fei
中科院分区：
文献类型：
--
作者：
Wang, Ling-xia;Wang, Jing;Shen, Yu-fei
Lin28是一种小分子RNA结合蛋白，在调控发育进程、干细胞重编程以及肿瘤发生过程中发挥着重要作用。然而，翻译后修饰对Lin28活性影响的重要意义尚未完全明晰。在本研究中，我们证实PCAF可直接与Lin28相互作用并使其乙酰化。我们还发现，Lin28的乙酰化状态可被去乙酰化酶SIRT1特异性逆转。这些研究结果表明，PCAF/SIRT1平衡在调控Lin28活性方面起着重要作用。此外，我们发现Lin28的冷休克结构域是PCAF介导的乙酰化修饰的主要靶点，这会导致Lin28蛋白水平显著降低，同时成熟let - 7a水平升高。本研究首次证明，翻译后修饰在let - 7a生物合成过程中对Lin28活性具有调控作用，为胚胎干细胞中Lin28的调控机制以及肿瘤发生机制的研究提供了新的思路。（2014年，爱思唯尔出版集团版权所有。）
Lin28 is a small RNA-binding protein that plays an important role in regulating developmental timing, stem cell reprogramming, and oncogenesis. However, the significance of the effect of post-translational modifications on Lin28 activity is not fully understood. In this study, we demonstrated that PCAF directly interacted with and acetylated Lin28. We also showed that the acetylation of Lin28 can be specifically reversed by the deacetylase SIRT1. These findings suggest that the PCAF/SIRT1 balance plays an important role in regulating Lin28 activity. Furthermore, we found that the cold shock domain of Lin28 is the major target of PCAF-mediated acetylation, which leads to a severe reduction in the Lin28 protein levels and an increase in the level of mature let-7a. This study provides the first demonstration that post-translational modification regulates Lin28 activity during let-7a biogenesis and sheds light on the regulation of Lin28 in ES cells and carcinogenesis. (C) 2014 Elsevier B.V. All rights reserved.