JAMP optimizes ERAD to protect cells from unfolded proteins Journal Article


Authors: Tcherpakov, M.; Broday, L.; Delaunay, A.; Kadoya, T.; Khurana, A.; Erdjument-Bromage, H.; Tempst, P.; Qiu, X. B.; Demartino, G. N.; Ronai, Z.
Article Title: JAMP optimizes ERAD to protect cells from unfolded proteins
Abstract: Clearance of misfolded proteins from the ER is central for maintenance of cellular homeostasis. This process requires coordinated recognition, ER-cytosol translocation, and finally ubiquitination-dependent proteasomal degradation. Here, we identify an ER resident seven-transmembrane protein (jAMP) that links ER chaperones, channel proteins, ubiquitin ligases, and 26S proteasome subunits, thereby optimizing degradation of misfolded proteins. Elevated JAMP expression promotes localization of proteasomes at the ER, with a concomitant effect on degradation of specific ER-resident misfolded proteins, whereas inhibiting JAMP promotes the opposite response. Correspondingly, a jamp-1 deleted Caenorhabditis elegans strain exhibits hypersensitivity to ER stress and increased UPR. Using biochemical and genetic approaches, we identify JAMP as important component for coordinated clearance of misfolded proteins from the ER. © 2008 by The American Society for Cell Biology.
Keywords: controlled study; protein expression; carrier protein; unclassified drug; human cell; nonhuman; ubiquitin; protein localization; mouse; animal; metabolism; animals; mice; complex formation; proteasome; proteasome endopeptidase complex; protein degradation; pathology; hela cell; hela cells; endoplasmic reticulum; protein processing; protein processing, post-translational; membrane glycoproteins; carrier proteins; membrane protein; protein transport; multiprotein complexes; caenorhabditis elegans; protein subunit; protein subunits; protein folding; cell protection; ligase; chaperone; multiprotein complex; protein jamp; jamp protein, mouse; endoplasmic reticulum stress
Journal Title: Molecular Biology of the Cell
Volume: 19
Issue: 11
ISSN: 1059-1524
Publisher: The American Society for Cell Biology  
Date Published: 2008-11-01
Start Page: 5019
End Page: 5028
Language: English
DOI: 10.1091/mbc.E08-08-0839
PUBMED: 18784250
PROVIDER: scopus
PMCID: PMC2575167
DOI/URL:
Notes: --- - "Cited By (since 1996): 4" - "Export Date: 17 November 2011" - "CODEN: MBCEE" - "Source: Scopus"
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  1. Paul J Tempst
    324 Tempst