Access

You are not currently logged in.

Access your personal account or get JSTOR access through your library or other institution:

login

Log in to your personal account or through your institution.

If You Use a Screen Reader

This content is available through Read Online (Free) program, which relies on page scans. Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.

A Subset of Membrane-Associated Proteins Is Ubiquitinated in Response to Mutations in the Endoplasmic Reticulum Degradation Machinery

Amy L. Hitchcock, Kathryn Auld, Steven P. Gygi and Pamela A. Silver
Proceedings of the National Academy of Sciences of the United States of America
Vol. 100, No. 22 (Oct. 28, 2003), pp. 12735-12740
Stable URL: http://www.jstor.org/stable/3148029
Page Count: 6
  • Read Online (Free)
  • Subscribe ($19.50)
  • Cite this Item
Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
A Subset of Membrane-Associated Proteins Is Ubiquitinated in Response to Mutations in the Endoplasmic Reticulum Degradation Machinery
Preview not available

Abstract

Ubiquitination of membrane-associated proteins can direct their proteasome-mediated degradation or activation at the endoplasmic reticulum (ER), as well as their endocytosis and intracellular sorting. However, the full spectrum of ubiquitinated membrane proteins has not been determined. Here we combined proteomic analysis with yeast genetics to identify 211 ubiquitinated membrane-associated proteins in Saccharomyces cerevisiae and map >30 precise sites of ubiquitination. Major classes of identified ubiquitinated proteins include ER-resident membrane proteins, plasma membrane-localized permeases, receptors, and enzymes, and surprisingly, components of the actin cytoskeleton. By determining the differential abundance of ubiquitinated proteins in yeast mutated for NPL4 and UBC7, which are major components of ER-associated degradation (ERAD), we furthermore were able to classify 83 of these identified ubiquitinated membrane proteins as potential endogenous substrates of the ERAD pathway. These substrates are highly enriched for proteins that localize to or transit through the ER. Interestingly, we also identified novel membrane-bound transcription factors that may be subject to ubiquitin/proteasome-mediated cleavage and activation at the ER membrane.

Page Thumbnails

  • Thumbnail: Page 
[12735]
    [12735]
  • Thumbnail: Page 
12736
    12736
  • Thumbnail: Page 
12737
    12737
  • Thumbnail: Page 
12738
    12738
  • Thumbnail: Page 
12739
    12739
  • Thumbnail: Page 
12740
    12740