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Genome-wide screen identifies a novel p97/CDC-48-dependent pathway regulating ER-stress-induced gene transcription

dc.contributor.authorMARZA, Esther
dc.contributor.authorTAOUJI, Said
dc.contributor.authorBARROSO, Kim
dc.contributor.authorRAYMOND, Anne-Aurelie
dc.contributor.authorGUIGNARD, Leo
dc.contributor.authorBONNEU, Marc
dc.contributor.authorPALLARES-LUPON, Nestor
dc.contributor.authorDUPUY, Jean-William
dc.contributor.authorFERNANDEZ-ZAPICO, Martin E.
dc.contributor.authorROSENBAUM, Jean
dc.contributor.authorPALLADINO, Francesca
dc.contributor.authorDUPUY, Denis
dc.contributor.authorCHEVET, Eric
dc.date.accessioned2020-09-03T08:02:01Z
dc.date.available2020-09-03T08:02:01Z
dc.date.issued2015
dc.identifier.issn1469-221X
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/10952
dc.description.abstractEnThe accumulation of misfolded proteins in the endoplasmic reticulum (ER) activates the Unfolded Protein Response (UPRER) to restore ER homeostasis. The AAA(+) ATPase p97/CDC-48 plays key roles in ER stress by promoting both ER protein degradation and transcription of UPRER genes. Although the mechanisms associated with protein degradation are now well established, the molecular events involved in the regulation of gene transcription by p97/CDC-48 remain unclear. Using a reporter-based genome-wide RNAi screen in combination with quantitative proteomic analysis in Caenorhabditis elegans, we have identified RUVB-2, a AAA(+) ATPase, as a novel repressor of a subset of UPRER genes. We show that degradation of RUVB-2 by CDC-48 enhances expression of ER stress response genes through an XBP1-dependent mechanism. The functional interplay between CDC-48 and RUVB-2 in controlling transcription of select UPRER genes appears conserved in human cells. Together, these results describe a novel role for p97/CDC-48, whereby its role in protein degradation is integrated with its role in regulating expression of ER stress response genes.
dc.language.isoen
dc.title.enGenome-wide screen identifies a novel p97/CDC-48-dependent pathway regulating ER-stress-induced gene transcription
dc.typeArticle de revue
dc.subject.halChimie/Matériaux
bordeaux.journalEMBO reports
bordeaux.page332-340
bordeaux.volume16
bordeaux.hal.laboratoriesInstitut de Chimie & de Biologie des Membranes & des Nano-objets (CBMN) - UMR 5248*
bordeaux.hal.laboratoriesInstitut de Chimie & de Biologie des Membranes & des Nano-objets (CBMN, UMR 5248)
bordeaux.issue3
bordeaux.institutionUniversité de Bordeaux
bordeaux.institutionBordeaux INP
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