Itch, an E3 ligase of Oct4, is required for embryonic stem cell self-renewal and pluripotency induction

Itch, an E3 ligase of Oct4, is required for embryonic stem cell self-renewal and pluripotency induction
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Itch 是 Oct4 的 E3 连接酶,是胚胎干细胞自我更新和多能性诱导所必需的

DOI:
10.1002/jcp.24297
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发表时间:
2013-07-01
影响因子:
5.6
通讯作者:
Jin, Ying
Jin, Ying
中科院分区:
生物学2区
文献类型:
--
作者:
Liao, Bing;Zhong, Xiaoming;Jin, Ying

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Itch是一种C2-WW-HECT结构域泛素E3连接酶,在多种生物学过程中发挥重要作用。然而,它在胚胎干细胞(ESC)中的作用仍然未知。在这里,我们报告说,瘙痒相互作用和目标多能相关转录因子Oct 4的泛素化。此外,Itch增强了Oct 4的转录活性,并依赖于其催化活性控制Oct 4蛋白的稳定性。重要的是,沉默Itch表达损害ESC自我更新能力和体细胞重编程效率。综上所述,我们的研究确定瘙痒作为Oct 4稳定性和转录活性的调节剂,建立了E3连接酶和多能性调节之间的功能联系。J.细胞。228:14431451,2013。(c)2012 Wiley Periodicals,Inc.
Itch, a C2-WW-HECT domain ubiquitin E3 ligase, plays an important role in various biological processes. However, its role in embryonic stem cells (ESCs) remains unknown. Here, we report that Itch interacts with and targets pluripotency-associated transcription factor Oct4 for ubiquitination. Moreover, Itch enhances Oct4 transcriptional activities and controls Oct4 protein stability dependent on its catalytic activity. Importantly, silencing Itch expression compromises ESC self-renewal capacity and somatic cell reprogramming efficiency. Taken together, our study identifies Itch as a regulator of Oct4 stability and transcriptional activity, establishing a functional link between an E3 ligase and the regulation of pluripotency. J. Cell. Physiol. 228: 14431451, 2013. (c) 2012 Wiley Periodicals, Inc.