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DCP1A, a MEK substrate, regulates the self-renewal and differentiation of mouse embryonic stem cells

Published:12 December 2024 DOI: 10.1016/j.celrep.2024.115058 PMID: 39671288
Jiayu Yu,?Nannan Zhao,?Yuying Wang,?Nan Ding,?Zhenchang Guo,?Zichan He,?Qingye Zhang,?Jingai Zhang,?Xiaoqiong Yang,?Ming Zhang,?Xiaoling Du,?Kai Zhang,?Lingyi Chen

Abstract

Mitogen-activated extracellular signal-regulated kinase (MEK) inhibitors are widely applied to maintain pluripotency, while prolonged MEK inhibition compromises the developmental potential of mouse embryonic stem cells (ESCs). To understand the mechanism of MEK in pluripotency maintenance, we first demonstrated that MEK regulates gene expression at post-transcriptional steps. Consistently, many of the 66 MEK substrates identified by quantitative phosphoproteomics analysis are involved in RNA processing. We further confirmed that MEK1 phosphorylates S563 of DCP1A, an mRNA decapping cofactor and processing body (P body) component. DCP1A, as well as two other P body components, EDC4 and DCP2, are required for the self-renewal and differentiation of ESCs, indicating the role of P bodies in ESCs. Dephosphorylation of DCP1A S563 facilitates both self-renewal and differentiation of ESCs through promoting P body formation and RNA storage. In summary, our study identified 66 MEK substrates supporting the extracellular signal-regulated kinase (ERK)-independent function of MEK and revealed that DCP1A, phosphorylated by MEK, regulates ESC self-renewal and differentiation through modulating P body formation.

Substances (9)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Dimethyl sulfoxide 67-68-5 C2H6OS 1924 suppliers $5.00-$120900.00
L-Glutamine 56-85-9 C5H10N2O3 1440 suppliers $5.00-$11460.00
Formaldehyde 50-00-0 CH2O 901 suppliers $10.00-$1760.00
Paraformaldehyde 30525-89-4 (CH2O)x 768 suppliers $17.00-$1458.00
Proteinase K 39450-01-6 C29H27N2O12P 726 suppliers $48.00-$10680.00
Phenylmethylsulfonyl fluoride 329-98-6 C7H7FO2S 602 suppliers $5.00-$2875.00
Doxycycline 564-25-0 C22H24N2O8 375 suppliers Inquiry
PD 0325901 391210-10-9 C16H14F3IN2O4 281 suppliers $8.00-$3990.00
PUROMYCIN 53-79-2 C22H29N7O5 146 suppliers $39.00-$1200.00

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