Cycloheximide Inhibits Actin Cytoskeletal Dynamics by Suppressing Signaling via RhoA

J Cell Biochem. 2016 Dec;117(12):2886-2898. doi: 10.1002/jcb.25601. Epub 2016 Aug 16.

Abstract

Genome-wide screening of the yeast Saccharomyces cerevisiae knockout collection was used to characterize chemical-genetic interactions of cycloheximide (CHX). The results showed that while the act1Δ mutant was the only deletion mutant in the heterozygous essential gene deletion collection that showed hypersensitivity to sub-inhibitory concentrations of CHX, deletion of nonessential genes that work in concert with either cytoplasmic or nuclear actin in the homozygous deletion collection also highly sensitized yeast to CHX. Fluorescence microscopy analysis revealed that CHX disrupts filamentous actin structures and fluid phase endocytosis in the yeast cell. It also showed that CHX disrupts transforming growth factor-β1 (TGF-β1)-induced actin reorganization and polygonal architecture of microfilaments in mammalian cells. This inhibitory effect is mediated, at least in part, through the actin dynamics signaling pathway via suppression of activation of the small GTPase RhoA. J. Cell. Biochem. 117: 2886-2898, 2016. © 2016 Wiley Periodicals, Inc.

Keywords: ACTIN CYTOSKELETON; CYCLOHEXIMIDE; MICROFILAMENTS; SMALL GTPase RhoA; YEAST KNOCKOUT COLLECTION.

MeSH terms

  • Actin Cytoskeleton / drug effects*
  • Cells, Cultured
  • Cycloheximide / pharmacology*
  • Endocytosis / drug effects
  • Humans
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / antagonists & inhibitors*
  • Saccharomyces cerevisiae Proteins / metabolism
  • Signal Transduction / drug effects*
  • rhoA GTP-Binding Protein / antagonists & inhibitors*
  • rhoA GTP-Binding Protein / metabolism

Substances

  • Saccharomyces cerevisiae Proteins
  • Cycloheximide
  • rhoA GTP-Binding Protein