Serum response factor-cofactor interactions and their implications in disease

FEBS J. 2021 May;288(10):3120-3134. doi: 10.1111/febs.15544. Epub 2020 Sep 12.

Abstract

Serum response factor (SRF), a member of the Mcm1, Agamous, Deficiens, and SRF (MADS) box transcription factor, is widely expressed in all cell types and plays a crucial role in the physiological function and development of diseases. SRF regulates its downstream genes by binding to their CArG DNA box by interacting with various cofactors. However, the underlying mechanisms are not fully understood, therefore attracting increasing research attention due to the importance of this topic. This review's objective is to discuss the new progress in the studies of the molecular mechanisms involved in the activation of SRF and its impacts in physiological and pathological conditions. Notably, we summarized the recent studies on the interaction of SRF with its two main types of cofactors belonging to the myocardin families of transcription factors and the members of the ternary complex factors. The knowledge of these mechanisms will create new opportunities for understanding the dynamics of many traits and disease pathogenesis especially, cardiovascular diseases and cancer that could serve as targets for pharmacological control and treatment of these diseases.

Keywords: binding; cofactors; mechanisms; myocardin; serum response factor; transcription.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Actin Cytoskeleton / metabolism
  • Actin Cytoskeleton / pathology
  • Animals
  • Apoptosis / genetics
  • Cardiovascular Diseases / genetics*
  • Cardiovascular Diseases / metabolism
  • Cardiovascular Diseases / pathology
  • Cell Proliferation
  • DNA / genetics
  • DNA / metabolism
  • Gene Expression Regulation
  • Humans
  • Mice
  • Neoplasms / genetics*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Protein Binding
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Serum Response Factor / genetics*
  • Serum Response Factor / metabolism
  • Signal Transduction
  • Stress, Physiological
  • Ternary Complex Factors / genetics*
  • Ternary Complex Factors / metabolism
  • Trans-Activators / genetics*
  • Trans-Activators / metabolism
  • Transcription, Genetic*

Substances

  • Nuclear Proteins
  • Protein Isoforms
  • SRF protein, human
  • Serum Response Factor
  • Ternary Complex Factors
  • Trans-Activators
  • myocardin
  • DNA