RRC ID 4216
Author Caruso ME, Jenna S, Bouchecareilh M, Baillie DL, Boismenu D, Halawani D, Latterich M, Chevet E.
Title GTPase-mediated regulation of the unfolded protein response in Caenorhabditis elegans is dependent on the AAA+ ATPase CDC-48.
Journal Mol. Cell. Biol.
Abstract When endoplasmic reticulum (ER) homeostasis is perturbed, an adaptive mechanism is triggered and named the unfolded protein response (UPR). Thus far, three known UPR signaling branches (IRE-1, PERK, and ATF-6) mediate the reestablishment of ER functions but can also lead to apoptosis if ER stress is not alleviated. However, the understanding of the molecular mechanisms integrating the UPR to other ER functions, such as membrane traffic or endomembrane signaling, remains incomplete. We consequently sought to identify new regulators of UPR-dependent transcriptional mechanisms and focused on a family of proteins known to mediate, among other, ER-related functions: the small GTP-binding proteins of the RAS superfamily. To this end, we used transgenic UPR reporter Caenorhabditis elegans strains as a model to specifically silence small-GTPase expression. We show that the Rho subfamily member CRP-1 is an essential component of UPR-induced transcriptional events through its physical and genetic interactions with the AAA+ ATPase CDC-48. In addition, we describe a novel signaling module involving CRP-1 and CDC-48 which may directly link the UPR to DNA remodeling and transcription control.
Volume 28(13)
Pages 4261-74
Published 2008-7
DOI 10.1128/MCB.02252-07
PII MCB.02252-07
PMID 18458060
PMC PMC2447140
MeSH Adenosine Triphosphatases / metabolism* Animals Azetidinecarboxylic Acid / pharmacology Caenorhabditis elegans / cytology Caenorhabditis elegans / drug effects Caenorhabditis elegans / enzymology* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Cell Cycle Proteins / metabolism* Dithiothreitol / pharmacology Endoplasmic Reticulum / drug effects Endoplasmic Reticulum / enzymology Endoplasmic Reticulum / pathology GTP Phosphohydrolases / metabolism* Gene Expression Regulation / drug effects Gene Silencing / drug effects Green Fluorescent Proteins / metabolism Intestinal Mucosa / metabolism Intestines / drug effects Multiprotein Complexes / metabolism Mutation / genetics Promoter Regions, Genetic / genetics Protein Binding / drug effects Protein Folding* Thapsigargin / pharmacology Transcription, Genetic / drug effects Tunicamycin / pharmacology Valosin Containing Protein rho GTP-Binding Proteins / metabolism
IF 3.813
Times Cited 29
C.elegans tm544