MK2 promotes Tfcp2l1 degradation via β-TrCP ubiquitin ligase to regulate mouse embryonic stem cell self-renewal

Summary: Tfcp2l1 can maintain mouse embryonic stem cell (mESC) self-renewal. However, it remains unknown how Tfcp2l1 protein stability is regulated. Here, we demonstrate that β-transducin repeat-containing protein (β-TrCP) targets Tfcp2l1 for ubiquitination and degradation in a mitogen-activated pro...

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Autores principales:	Yan Zhang, Huiwen Ding, Xiaoxiao Wang, Xin Wang, Shengpeng Wan, Anchun Xu, Ruoyi Gan, Shou-Dong Ye
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	embryonic stem cells self-renewal degradation Tfcp2l1 MK2 β-TrCP1 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/219f32317c2745a6baa0c76ec945fb8f
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spelling	oai:doaj.org-article:219f32317c2745a6baa0c76ec945fb8f2021-11-04T04:29:43ZMK2 promotes Tfcp2l1 degradation via β-TrCP ubiquitin ligase to regulate mouse embryonic stem cell self-renewal2211-124710.1016/j.celrep.2021.109949https://doaj.org/article/219f32317c2745a6baa0c76ec945fb8f2021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2211124721014261https://doaj.org/toc/2211-1247Summary: Tfcp2l1 can maintain mouse embryonic stem cell (mESC) self-renewal. However, it remains unknown how Tfcp2l1 protein stability is regulated. Here, we demonstrate that β-transducin repeat-containing protein (β-TrCP) targets Tfcp2l1 for ubiquitination and degradation in a mitogen-activated protein kinase (MAPK)-activated protein kinase 2 (MK2)-dependent manner. Specifically, β-TrCP1 and β-TrCP2 recognize and ubiquitylate Tfcp2l1 through the canonical β-TrCP-binding motif DSGDNS, in which the serine residues have been phosphorylated by MK2. Point mutation of serine-to-alanine residues reduces β-TrCP-mediated ubiquitylation and enhances the ability of Tfcp2l1 to promote mESC self-renewal while repressing the speciation of the endoderm, mesoderm, and trophectoderm. Similarly, inhibition of MK2 reduces the association of Tfcp2l1 with β-TrCP1 and increases the self-renewal-promoting effects of Tfcp2l1, whereas overexpression of MK2 or β-TrCP genes decreases Tfcp2l1 protein levels and induces mESC differentiation. Collectively, our study reveals a posttranslational modification of Tfcp2l1 that will expand our understanding of the regulatory network of stem cell pluripotency.Yan ZhangHuiwen DingXiaoxiao WangXin WangShengpeng WanAnchun XuRuoyi GanShou-Dong YeElsevierarticleembryonic stem cellsself-renewaldegradationTfcp2l1MK2β-TrCP1Biology (General)QH301-705.5ENCell Reports, Vol 37, Iss 5, Pp 109949- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	embryonic stem cells self-renewal degradation Tfcp2l1 MK2 β-TrCP1 Biology (General) QH301-705.5
spellingShingle	embryonic stem cells self-renewal degradation Tfcp2l1 MK2 β-TrCP1 Biology (General) QH301-705.5 Yan Zhang Huiwen Ding Xiaoxiao Wang Xin Wang Shengpeng Wan Anchun Xu Ruoyi Gan Shou-Dong Ye MK2 promotes Tfcp2l1 degradation via β-TrCP ubiquitin ligase to regulate mouse embryonic stem cell self-renewal
description	Summary: Tfcp2l1 can maintain mouse embryonic stem cell (mESC) self-renewal. However, it remains unknown how Tfcp2l1 protein stability is regulated. Here, we demonstrate that β-transducin repeat-containing protein (β-TrCP) targets Tfcp2l1 for ubiquitination and degradation in a mitogen-activated protein kinase (MAPK)-activated protein kinase 2 (MK2)-dependent manner. Specifically, β-TrCP1 and β-TrCP2 recognize and ubiquitylate Tfcp2l1 through the canonical β-TrCP-binding motif DSGDNS, in which the serine residues have been phosphorylated by MK2. Point mutation of serine-to-alanine residues reduces β-TrCP-mediated ubiquitylation and enhances the ability of Tfcp2l1 to promote mESC self-renewal while repressing the speciation of the endoderm, mesoderm, and trophectoderm. Similarly, inhibition of MK2 reduces the association of Tfcp2l1 with β-TrCP1 and increases the self-renewal-promoting effects of Tfcp2l1, whereas overexpression of MK2 or β-TrCP genes decreases Tfcp2l1 protein levels and induces mESC differentiation. Collectively, our study reveals a posttranslational modification of Tfcp2l1 that will expand our understanding of the regulatory network of stem cell pluripotency.
format	article
author	Yan Zhang Huiwen Ding Xiaoxiao Wang Xin Wang Shengpeng Wan Anchun Xu Ruoyi Gan Shou-Dong Ye
author_facet	Yan Zhang Huiwen Ding Xiaoxiao Wang Xin Wang Shengpeng Wan Anchun Xu Ruoyi Gan Shou-Dong Ye
author_sort	Yan Zhang
title	MK2 promotes Tfcp2l1 degradation via β-TrCP ubiquitin ligase to regulate mouse embryonic stem cell self-renewal
title_short	MK2 promotes Tfcp2l1 degradation via β-TrCP ubiquitin ligase to regulate mouse embryonic stem cell self-renewal
title_full	MK2 promotes Tfcp2l1 degradation via β-TrCP ubiquitin ligase to regulate mouse embryonic stem cell self-renewal
title_fullStr	MK2 promotes Tfcp2l1 degradation via β-TrCP ubiquitin ligase to regulate mouse embryonic stem cell self-renewal
title_full_unstemmed	MK2 promotes Tfcp2l1 degradation via β-TrCP ubiquitin ligase to regulate mouse embryonic stem cell self-renewal
title_sort	mk2 promotes tfcp2l1 degradation via β-trcp ubiquitin ligase to regulate mouse embryonic stem cell self-renewal
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/219f32317c2745a6baa0c76ec945fb8f
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MK2 promotes Tfcp2l1 degradation via β-TrCP ubiquitin ligase to regulate mouse embryonic stem cell self-renewal

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