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MiR-322/424 and -503 Are Induced during Muscle Differentiation and Promote Cell Cycle Quiescence and Differentiation by Down-Regulation of Cdc25A

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Sarkar, Sukumar, Dey, Bijan K., Dutta, Anindya·2010·Molecular Biology of the Cell

Abstract

Induction of a G1 phase cell cycle arrest, caused primarily by the inhibition of cyclin-dependent-kinase 2 (cdk2), is a critical step in the differentiation of myoblasts into myotubes. Here, we report that two microRNAs, miR-322/424 and miR-503, are induced and promote cdk2 inhibition during myogenesis. These microRNAs down-regulate Cdc25A, the phosphatase responsible for removing inhibitory phosphorylation of cdk2, both in myoblasts differentiating into myotubes and in nonmuscle cells. Cdc25A is down-regulated during muscle differentiation by multiple pathways: action of these two microRNAs, proteasomal degradation of Cdc25A protein and transcriptional repression. Overexpression of Cdc25A or of cdk2 with mutations on T14 and Y15 (cdk2-AF), so that it cannot be inhibited by phosphorylation, decreases differentiation and differentiation-induced cell cycle quiescence. Introduction of miR-322/424 and miR-503 in heterologous cancer cells induces G1 arrest, which is also attenuated by overexpression of the cdk2-AF mutant. Until now Cdc25A and the inhibitory phosphorylation on T14 and Y15 of cdk2 have only been implicated in the intra-S phase checkpoint pathway after DNA damage. Our results reveal an unexpected role of Cdc25A down-regulation and the inhibitory phosphorylation of cdk2 T14 and Y15 in cell cycle quiescence during muscle differentiation and implicate two muscle differentiation-induced microRNAs in the process.

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Metadata

Authors
Sarkar, S., Dey, B. K., & Dutta, A.
Venue
Molecular Biology of the Cell
Published
2010-07
Volume
21
Issue
13
Pages
2138-2149
ISSN
  • 1059-1524 (ISSN-L)
  • 1939-4586
OpenAlex
W2123631180
Cited by
204
References
7
FWCI
7.56
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: MiR-322/424 and -503 Are Induced during Muscle Differentiation and Promote Cell Cycle Quiescence and Differentiation by Down-Regulation of Cdc25A. https://app.cochat.ai/papers/10.1091/mbc.e10-01-0062
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Sarkar, S., Dey, B. K., & Dutta, A. (2010). MiR-322/424 and -503 Are Induced during Muscle Differentiation and Promote Cell Cycle Quiescence and Differentiation by Down-Regulation of Cdc25A. Molecular Biology of the Cell. https://doi.org/10.1091/mbc.e10-01-0062

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