Regulating the regulators: Epigenetic, transcriptional, and post-translational regulation of RGS proteins

Cell Signal. 2018 Jan;42:77-87. doi: 10.1016/j.cellsig.2017.10.007. Epub 2017 Oct 16.


Regulators of G protein signaling (RGS) are a family of proteins classically known to accelerate the intrinsic GTPase activity of G proteins, which results in accelerated inactivation of heterotrimeric G proteins and inhibition of G protein coupled receptor signaling. RGS proteins play major roles in essential cellular processes, and dysregulation of RGS protein expression is implicated in multiple diseases, including cancer, cardiovascular and neurodegenerative diseases. The expression of RGS proteins is highly dynamic and is regulated by epigenetic, transcriptional and post-translational mechanisms. This review summarizes studies that report dysregulation of RGS protein expression in disease states, and presents examples of drugs that regulate RGS protein expression. Additionally, this review discusses, in detail, the transcriptional and post-transcriptional mechanisms regulating RGS protein expression, and further assesses the therapeutic potential of targeting these mechanisms. Understanding the molecular mechanisms controlling the expression of RGS proteins is essential for the development of therapeutics that indirectly modulate G protein signaling by regulating expression of RGS proteins.

Keywords: Epigenetics; MicroRNA; Post-translational modification; Proteasomal degradation; RGS; Regulator of G protein signaling; Therapeutics; Transcription factors.

Publication types

  • Review

MeSH terms

  • Animals
  • Azacitidine / therapeutic use
  • Benzodiazepines / therapeutic use
  • Cardiovascular Diseases / drug therapy*
  • Cardiovascular Diseases / genetics
  • Cardiovascular Diseases / metabolism
  • Cardiovascular Diseases / pathology
  • Drugs, Investigational / therapeutic use*
  • Epigenesis, Genetic*
  • GTP-Binding Proteins / genetics
  • GTP-Binding Proteins / metabolism
  • Humans
  • Hydroxamic Acids / therapeutic use
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Neurodegenerative Diseases / drug therapy*
  • Neurodegenerative Diseases / genetics
  • Neurodegenerative Diseases / metabolism
  • Neurodegenerative Diseases / pathology
  • Olanzapine
  • Protein Processing, Post-Translational*
  • RGS Proteins / agonists
  • RGS Proteins / antagonists & inhibitors
  • RGS Proteins / genetics*
  • RGS Proteins / metabolism
  • Signal Transduction
  • Vorinostat


  • Drugs, Investigational
  • Hydroxamic Acids
  • RGS Proteins
  • Benzodiazepines
  • Vorinostat
  • GTP-Binding Proteins
  • Azacitidine
  • Olanzapine