Transcriptional and post-transcriptional regulation of the genes encoding the small GTPases RhoA, RhoB, and RhoC: implications for the pathogenesis of human diseases

Cell Mol Life Sci. 2018 Jun;75(12):2111-2124. doi: 10.1007/s00018-018-2787-y. Epub 2018 Mar 2.

Abstract

Rho GTPases are highly conserved proteins that play critical roles in many cellular processes including actin dynamics, vesicular trafficking, gene transcription, cell-cycle progression, and cell adhesion. The main mode of regulation of Rho GTPases is through guanine nucleotide binding (cycling between an active GTP-bound form and an inactive GDP-bound form), but transcriptional, post-transcriptional, and post-translational modes of Rho regulation have also been described. In the present review, we summarize recent progress on the mechanisms that control the expression of the three members of the Rho-like subfamily (RhoA, RhoB, and RhoC) at the level of gene transcription as well as their post-transcriptional regulation by microRNAs. We also discuss the progress made in deciphering the mechanisms of cross-talk between Rho proteins and the transforming growth factor β signaling pathway and their implications for the pathogenesis of human diseases such as cancer metastasis and fibrosis.

Keywords: Rho GTPases; RhoA; RhoB; RhoC; Signaling cross talks; TGFβ; Transcriptional regulation; miRNAs.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Gene Expression Regulation*
  • Humans
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Signal Transduction
  • Transcriptional Activation*
  • Transforming Growth Factor beta / metabolism
  • rhoA GTP-Binding Protein / genetics*
  • rhoA GTP-Binding Protein / metabolism
  • rhoB GTP-Binding Protein / genetics*
  • rhoB GTP-Binding Protein / metabolism
  • rhoC GTP-Binding Protein / genetics*
  • rhoC GTP-Binding Protein / metabolism

Substances

  • MicroRNAs
  • Transforming Growth Factor beta
  • RHOA protein, human
  • RHOC protein, human
  • rhoA GTP-Binding Protein
  • rhoB GTP-Binding Protein
  • rhoC GTP-Binding Protein