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Originally published as MBC in Press, 10.1091/mbc.E08-08-0839 on September 10, 2008

Vol. 19, Issue 11, 5019-5028, November 2008

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JAMP Optimizes ERAD to Protect Cells from Unfolded Proteins

Marianna Tcherpakov*, Limor Broday{dagger}, Agnes Delaunay*, Takayuki Kadoya*, Ashwani Khurana*, Hediye Erdjument-Bromage{ddagger}, Paul Tempst{ddagger}, Xiao-Bo Qiu*, George N. DeMartino§, and Ze'ev Ronai*

*Signal Transduction Program, Burnham Institute for Medical Research, La Jolla, CA 92037; {dagger}Department of Cell and Developmental Biology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, 69978, Israel; {ddagger}Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021; and §Departments of Physiology and Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390

Submitted August 15, 2008; Revised August 21, 2008; Accepted August 28, 2008
Monitoring Editor: Jeffrey L. Brodsky

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.


This was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E08-08-0839) on September 10, 2008.

Address correspondence to: Ze'ev Ronai (ronai{at}burnham.org).




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