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    宋晓元

    • 教授 博士生导师 硕士生导师
    • 教师英文名称:Xiaoyuan Song
    • 电子邮箱:
    • 学历:博士研究生毕业
    • 办公地点:中国科学技术大学西校区科技东楼915
    • 学位:博士
    • 毕业院校:美国罗彻斯特大学
    • 学科:生物学
    • 2022-10-01曾获荣誉当选:“典赞 2022科普安徽”科普活动“年度科普作品”
    • 2021-05-01曾获荣誉当选:安徽省优秀科普作品一等奖
    • 2019-09-16曾获荣誉当选:王宽诚育才奖

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    Stub1 maintains proteostasis of master transcription factors in embryonic stem cells.

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    DOI码:10.1016/j.celrep.2022.110919

    发表刊物:Cell Reports

    关键字:CP: Molecular biology; CP: Stem cell research; Nanog; Oct4; Sox2; Stub1; differentiation; embryonic stem cells; induced pluripotent stem cells; pluripotency; ubiquitination.

    摘要:The pluripotency and differentiation states of embryonic stem cells (ESCs) are regulated by a set of core transcription factors, primarily Sox2, Oct4, and Nanog. Although their transcriptional regulation has been studied extensively, the contribution of posttranslational modifications in Sox2, Oct4, and Nanog are poorly understood. Here, using a CRISPR-Cas9 knockout library screen in murine ESCs, we identify the E3 ubiquitin ligase Stub1 as a negative regulator of pluripotency. Manipulation of Stub1 expression in murine ESCs shows that ectopic Stub1 expression significantly reduces the protein half-life of Sox2, Oct4, and Nanog. Mechanistic investigations reveal Stub1 catalyzes the polyubiquitination and 26S proteasomal degradation of Sox2 and Nanog through K48-linked ubiquitin chains and Oct4 via K63 linkage. Stub1 deficiency positively enhances somatic cell reprogramming and delays differentiation, whereas its enforced expression triggers ESC differentiation. The discovery of Stub1 as an integral pluripotency regulator strengthens our understanding of ESC regulation beyond conventional transcriptional control mechanisms.

    卷号:39

    期号:10

    是否译文:

    发表时间:2022-06-07