PIM2 regulates stemness through phosphorylation of 4E-BP1

Hongyan Sun; Jiani Cao; Lin Zhao; Shaohua Zhu; Shenghui Chen; Yaqiong Li; Bin Zhao; Tongbiao Zhao

doi:10.1016/j.scib.2017.04.018

PIM2 regulates stemness through phosphorylation of 4E-BP1

Sci Bull (Beijing). 2017 May 30;62(10):679-685. doi: 10.1016/j.scib.2017.04.018. Epub 2017 Apr 21.

Authors

Hongyan Sun¹, Jiani Cao², Lin Zhao³, Shaohua Zhu², Shenghui Chen¹, Yaqiong Li¹, Bin Zhao⁴, Tongbiao Zhao⁵

Affiliations

¹ State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Graduate University of Chinese Academy of Sciences, Beijing 100049, China.
² State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
³ State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Chinese Medicine Hospital in Linyi City, Linyi 276600, China.
⁴ Life Sciences Institute, Zhejiang University, Hangzhou 310058, China.
⁵ State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Graduate University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: tbzhao@ioz.ac.cn.

PMID: 36659438
DOI: 10.1016/j.scib.2017.04.018

Abstract

Embryonic stem cells (ESCs) can undergo unlimited self-renewal and maintain pluripotency to differentiate into any cell type of the three germ layers. Extensive studies have shown ESC identity is regulated by transcription factors, epigenetic regulators and multiple signal transduction pathways. However, the kinase regulation of pluripotency is not well understood. Here we show that the serine/threonine kinase PIM2, which is highly expressed in ESCs but not in somatic cells, functions as a crucial stemness regulator in ESCs. Knockout of Pim2 inhibits the self-renewal and differentiation capability of ESCs. Mechanistic studies identified that PIM2 can directly phosphorylate 4E-BP1, leading to release of eIF4E which facilitates the translation of pluripotent genes in ESCs. Our study highlights a novel kinase cascade pathway for ESC identity maintenance.

Keywords: 4E-BP1; ESC; Phosphorylation; Pim2; Stemness.