biostudies-literatureNielsen JCFrancis Crick InstituteCancer Research UKHorizon 2020 Framework ProgrammeMedical Research CouncilWellcome Trustjcs264444https://www.ebi.ac.uk/biostudies/studies/S-EPMC12813672biostudies-literatureUnknown138(24)Serum response factor (SRF) and its cofactors, myocardin-related transcription factors A and B (MRTF-A and MRTF-B, respectively), regulate transcription of numerous cytoskeletal structural and regulatory genes, and most MRTF/SRF inactivation phenotypes reflect deficits in cytoskeletal dynamics. We show that MRTF-SRF activity is required for effective proliferation of both primary and immortalised fibroblast and epithelial cells. Cells lacking the MRTFs or SRF proliferate very slowly, express elevated levels of senescence-associated secretory phenotype (SASP) factors and senescence-associated β-galactosidase activity, and inhibit proliferation of co-cultured primary wild-type cells. They exhibit decreased levels of CDK1 and CKS2 proteins, and elevated levels of CDK inhibitors, usually p27 (Journal of cell scienceMRTF-dependent cytoskeletal dynamics drive efficient cell cycle progression.PMC12813672897131CC2102Benito-Jardon MNielsen JCTreisman RChristo Petrela NBellamy SDiring JfalseMRTF-dependent cytoskeletal dynamics drive efficient cell cycle progression.Serum response factor (SRF) and its cofactors, myocardin-related transcription factors A and B (MRTF-A and MRTF-B, respectively), regulate transcription of numerous cytoskeletal structural and regulatory genes, and most MRTF/SRF inactivation phenotypes reflect deficits in cytoskeletal dynamics. We show that MRTF-SRF activity is required for effective proliferation of both primary and immortalised fibroblast and epithelial cells. Cells lacking the MRTFs or SRF proliferate very slowly, express elevated levels of senescence-associated secretory phenotype (SASP) factors and senescence-associated β-galactosidase activity, and inhibit proliferation of co-cultured primary wild-type cells. They exhibit decreased levels of CDK1 and CKS2 proteins, and elevated levels of CDK inhibitors, usually p27 (2025-01-01T00:00:00Z2025 Dec2026-06-13T04:53:08.339Z2026-06-13T03:08:34.047ZS-EPMC128136724120079310.1242/jcs.264444