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MRTF-dependent cytoskeletal dynamics drive efficient cell cycle progression.

Julie C Nielsen1, Maria Benito-Jardon1, Noel Christo Petrela1

  • 1Signalling and transcription Laboratory, Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.

Journal of Cell Science
|November 7, 2025
PubMed
Summary
This summary is machine-generated.

Serum response factor (SRF) and myocardin-related transcription factors (MRTF) are crucial for cell proliferation and cytoskeletal dynamics. Their absence leads to slow growth, senescence, and impaired cell cycle progression.

Keywords:
Cell cycleCytoskeletonMKL1MRTF-AMRTF-BQuiescenceSRFSenescence

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Serum response factor (SRF) and its cofactors, myocardin-related transcription factors A and B (MRTF-A and MRTF-B), regulate genes involved in cytoskeletal structure and dynamics.
  • Deficits in cytoskeletal dynamics are often observed in conditions where MRTF/SRF activity is compromised.

Purpose of the Study:

  • To investigate the role of MRTF-SRF activity in cell proliferation and the underlying molecular mechanisms.
  • To determine if MRTF-SRF signaling is essential for cell cycle progression, particularly in contexts requiring high cellular contractility.

Main Methods:

  • Utilized primary and immortalized fibroblast and epithelial cells lacking MRTFs or SRF.
  • Analyzed cell proliferation rates, senescence markers (SASP factors, β-galactosidase activity), and protein levels (CDK1, CKS2, p27).
  • Investigated the effects of serum deprivation and inhibition of Rho kinases (ROCKs) or myosin ATPase on wild-type cells.

Main Results:

  • Cells lacking MRTFs or SRF exhibited significantly reduced proliferation, elevated senescence markers, and decreased levels of CDK1 and CKS2, with increased CDK inhibitors like p27.
  • These phenotypes were reversible upon MRTF-A re-expression and mimicked in wild-type cells under serum deprivation.
  • Inhibition of cytoskeletal dynamics via ROCKs or myosin ATPase induced similar proliferative defects, highlighting the role of contractility.

Conclusions:

  • MRTF-SRF activity is essential for effective cell proliferation in fibroblasts and epithelial cells.
  • The MRTF-SRF pathway influences cell cycle progression through regulation of key cell cycle proteins and cytoskeletal contractility.
  • MRTF-SRF signaling is likely required for cell cycle transitions in environments demanding significant cellular contractility.