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  Myocardin related transcription factors are required for coordinated cell cycle progression

Shaposhnikov, D., Kuffer, C., Storchova, Z., & Posern, G. (2013). Myocardin related transcription factors are required for coordinated cell cycle progression. CELL CYCLE, 12(11), 1762-1772. doi:10.4161/cc.24839.

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 Creators:
Shaposhnikov, Dmitry1, Author
Kuffer, Christian2, Author           
Storchova, Zuzana2, Author           
Posern, Guido1, Author
Affiliations:
1external, ou_persistent22              
2Storchova, Zuzana / Maintenance of Genome Stability, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565171              

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Free keywords: SERUM RESPONSE FACTOR; SMOOTH-MUSCLE DIFFERENTIATION; SIGNAL-TRANSDUCTION; GENE-TRANSCRIPTION; ACTIN DYNAMICS; GROWTH-FACTOR; RHO GTPASES; FACTOR-B; KINASE; SRFMrtf; actin; transcription; p27Kip1; aneuploidy; apoptosis;
 Abstract: Myocardin related transcription factors A and B (MRTFs) activate serum response factor-driven transcription in response to Rho signaling and changes in actin dynamics. Myocardin and MRTFs have been implicated in anti-proliferative effects on a range of cell types. the precise mechanisms, however, remained elusive. We employed double knockdown of MRTF-A and MRTF-B in NIH 3T3 fibroblasts to evaluate its effects on cell cycle progression and proliferation. We show that transient depletion of MRTFs conveys a modest anti-proliferative effect and impinges on normal cell cycle progression, resulting in significantly shortened G 1 phase and slightly extended S and G 2 phase under normal growth conditions. Under serum-starved conditions we observed aberrant entry into the S and G 2 phases without subsequent cell division. this was accompanied by downregulation of cyclin-CDK inhibitors p27Kip1, p18Ink4c and 19Ink4d as well as upregulation of p21Waf1 and cyclin D1. extended knockdown led to increased formation of micronuclei, while cells stably depleted of MRTFs tend to become aneuploid and polyploid. thus, MRTFs are required for accurate cell cycle progression and maintenance of genomic stability in fibroblast cells.

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Language(s): eng - English
 Dates: 2013
 Publication Status: Issued
 Pages: 11
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: ISI: 000330525900023
DOI: 10.4161/cc.24839
 Degree: -

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Title: CELL CYCLE
Source Genre: Journal
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Publ. Info: 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA : LANDES BIOSCIENCE
Pages: - Volume / Issue: 12 (11) Sequence Number: - Start / End Page: 1762 - 1772 Identifier: ISSN: 1538-4101