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.
authors.affiliation: Signal Transduction Program, Burnham Institute for Medical Research, La Jolla, CA 92037, USA.
authors.forename: Marianna
authors.initials: M
authors.lastname: Tcherpakov
authors.forename: Limor
authors.initials: L
authors.lastname: Broday
authors.forename: Agnes
authors.initials: A
authors.lastname: Delaunay
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kadoya
authors.forename: Ashwani
authors.initials: A
authors.lastname: Khurana
authors.forename: Hediye
authors.initials: H
authors.lastname: Erdjument-Bromage
authors.forename: Paul
authors.initials: P
authors.lastname: Tempst
authors.forename: Xiao-Bo
authors.initials: XB
authors.lastname: Qiu
authors.forename: George N
authors.initials: GN
authors.lastname: DeMartino
authors.forename: Ze'ev
authors.initials: Z
authors.lastname: Ronai
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism* / Q000473:pathology; D006367:HeLa Cells; D006801:Humans; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000378:metabolism*; D051379:Mice; D046912:Multiprotein Complexes / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D017510:Protein Folding; D011499:Protein Processing, Post-Translational; D021122:Protein Subunits / Q000378:metabolism; D021381:Protein Transport
chemical_list: D002352:Carrier Proteins; C505618:JAMP protein, mouse; D008562:Membrane Glycoproteins; D046912:Multiprotein Complexes; D021122:Protein Subunits; D046988:Proteasome Endopeptidase Complex
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