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.

journal_name

Mol Biol Cell

authors

Tcherpakov M,Broday L,Delaunay A,Kadoya T,Khurana A,Erdjument-Bromage H,Tempst P,Qiu XB,DeMartino GN,Ronai Z

doi

10.1091/mbc.e08-08-0839

subject

Has Abstract

pub_date

2008-11-01 00:00:00

pages

5019-28

issue

11

eissn

1059-1524

issn

1939-4586

pii

E08-08-0839

journal_volume

19

pub_type

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