Myocardin related transcription factors are required for coordinated cell cycle progression.
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.
['Shaposhnikov|Dmitry|D|', 'Kuffer|Christian|C|', 'Storchova|Zuzana|Z|', 'Posern|Guido|G|']
D000818:Animals D059447:Cell Cycle Checkpoints D049109:Cell Proliferation D002875:Chromosomes D019938:Cyclin D1 D050763:Cyclin-Dependent Kinase Inhibitor p18 D050764:Cyclin-Dependent Kinase Inhibitor p19 D050759:Cyclin-Dependent Kinase Inhibitor p21 D050760:Cyclin-Dependent Kinase Inhibitor p27 D015536:Down-Regulation D051379:Mice D041681:NIH 3T3 Cells D034622:RNA Interference D012333:RNA, Messenger D034741:RNA, Small Interfering D015534:Trans-Activators D014157:Transcription Factors D015854:Up-Regulation
transcription Mrtf actin p27Kip1 aneuploidy apoptosis