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

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.

Protective effects of oxymatrine against DSS-induced acute intestinal inflammation in mice via blocking the RhoA/ROCK signaling pathway

“…Rho kinase (ROCK) is a 160 kDa threonine/serine kinase made up of ROCK2 and ROCK1. ROCK1 and ROCK2 were initially identified as key effectors of RhoA, and through the phosphorylation of the downstream targets, these kinases regulate a wide range of physiological functions [21]. ROCK has many types of downstream targets, including myosin light chain (MLC), MLC phosphatase (MLCP) and myosin phosphatase-targeting subunit-1 (MYPT-1).…”

AGAP2: Modulating TGFβ1-Signaling in the Regulation of Liver Fibrosis

“…The small-GTPases of the Ras family including Rab, Ran and Rho GTPases are key components in the regulation of TGFβ1 signaling during TGFβ1 receptor endocytosis, Smad trafficking and cross-talk with the actin cytoskeleton, respectively [45][46][47]. A recent review describes the cross-talk between Rho proteins and the TGFβ1 signaling pathway and their implication for the pathogenesis of human diseases as fibrosis [48], and Ren et al [49] describe how endostatin inhibits TGFβ-induced fibrosis in HSC by modulating the RhoA/ROCK signal pathway.…”

Short-term angiotensin II treatment regulates cardiac nanomechanicsviamicrotubule modifications

“…Under these experimental conditions, the AngII effect on the transverse YM is caused by TGF-β1 trans-activation. Recently, Ras/ Rho has been shown to be a part of the downstream signaling pathway of TGF-β1 36 and that Rho is activated in neonatal cardiomyocytes following AngII treatment. 37 We analyzed whether this pathway plays a role in the cell's YM using a selective Rho kinase inhibitor, Y-27632.…”