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Nuclear receptor corepressor complexes in cancer: mechanism, function and regulation

Madeline M Wong1, Chun Guo1, Jinsong Zhang1

  • 1Department of Pharmacological & Physiological Science, Saint Louis University School of Medicine St. Louis, Missouri 63104.

American Journal of Clinical and Experimental Urology
|November 7, 2014
PubMed

Insights

Nuclear receptor corepressors, nuclear receptor corepressor (NCoR) and silencing mediator for retinoid and thyroid hormone receptors (SMRT), are implicated in cancer. Understanding their mechanisms is key for developing effective cancer therapies targeting these proteins.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Epigenetics

Background:

  • Nuclear receptor corepressors, NCoR and SMRT, regulate gene expression by interacting with various transcription factors, including those involved in hormone signaling.
  • Dysregulation of NCoR and SMRT is frequently observed in various cancers and leukemias, highlighting their potential role in tumorigenesis.
  • These corepressors form complexes with other proteins like HDAC3, TBL1, and GPS2, which also exhibit altered functions in cancer.

Purpose of the Study:

  • To review the current literature on the mechanisms, regulation, and functions of NCoR/SMRT complex components.
  • To explore the involvement of these core components in the pathogenesis of cancers and leukemias.
  • To assess the potential of NCoR/SMRT complexes as therapeutic targets for cancer treatment.

Main Methods:

  • Literature review and synthesis of existing research findings.
  • Analysis of molecular mechanisms underlying NCoR/SMRT complex formation and function.
  • Examination of the role of NCoR/SMRT in cancer and leukemia development.

Main Results:

  • NCoR and SMRT directly bind transcription factors, forming stable complexes with histone deacetylase 3, TBL1-related protein 1, and G-protein pathway suppressor 2.
  • The deregulated functions of NCoR, SMRT, and their interacting proteins are associated with various cancers and leukemias.
  • Evidence suggests that NCoR/SMRT complexes are promising targets for cancer therapy.

Conclusions:

  • NCoR/SMRT complexes play a significant role in the development and progression of cancers and leukemias.
  • Targeting NCoR/SMRT corepressors offers a potential therapeutic strategy for cancer treatment.
  • Further research is needed to elucidate the specific mechanisms of these corepressors in different cancer types to optimize therapeutic interventions.
Keywords:
GPS2HDAC3NCoRSMRTTBL1TBLR1cancercorepressortranscriptional repression

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