Steroid receptor coactivators: from basic research to translational opportunities

Yosef Gilad1, Sang Jun Han1,2, David M Lonard1,2

  • 1Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.

Endocrine Reviews
|February 20, 2026
PubMed

Insights

Nuclear receptors (NRs) are regulated by coregulators, not independent. The Steroid Receptor Coactivator (SRC) family, key regulators of NR function, are crucial therapeutic targets in physiology and oncology.

Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • Nuclear receptors (NRs) control gene expression but require coregulators.
  • Coregulators modulate NR activity, acting as key controllers of transcription.
  • The Steroid Receptor Coactivator (SRC) family is a dominant group of NR coregulators.

Purpose of the Study:

  • To outline the evolution of the nuclear receptor coregulation concept.
  • To highlight the central roles of SRCs in physiology and oncology.
  • To trace therapeutic strategies targeting SRC proteins.

Main Methods:

  • Literature review on nuclear receptor coregulation.
  • Analysis of the discovery and validation of NR coregulators.
  • Examination of SRC family's role in gene expression and disease.

Main Results:

  • The concept of NR coregulation predates experimental validation.
  • Coregulators, particularly SRCs, are essential for NR-mediated transcription.
  • SRCs play critical roles in physiological processes and cancer.

Conclusions:

  • The discovery of SRCs marked a milestone in understanding NR coregulation.
  • SRCs are vital targets for therapeutic intervention in various diseases.
  • Targeting SRCs offers promising strategies for physiological and oncological conditions.

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