Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text (PDF, 506K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Tuma, R. S. Search for Related Content PubMed Articles by Tuma, R. S. Related Collections Related Article Social Bookmarking                            What's this?

Signal for ER-associated degradation

CPY1 is a poor substrate for ERAD because it lacks a vital sugar.

A major pathway for misfolded proteins is the ER-associated degradation (ERAD) pathway. On page 73, Spear and Ng show that misfolding is not enough to target a protein to ERAD. Rather, particular sugar residues act as signals.

The team used a shortened CPY protein as a model unfolded protein. CPY1 lacked the terminal 154 amino acids of the protein. Surprisingly, it was retained in the ER, rather than being targeted for ERAD. Although CPY contains four N-glycosylation sites, the team found that if they disrupted the last site—the one missing in CPY1—the protein was retained in the ER.To further test whether a single glycan could act as a signal for degradation, the team created two novel mutations in the ERAD substrate proteinase A*. When they mutated the first of two N-glycosylation sites in the protein, it was retained in the ER, like CPY1; but mutating the second site had no effect.

The team has started to further narrow down the features of the glycosylation sites that act as ERAD-entry signals. They have preliminary evidence that it is a bipartite signal, with a polypeptide sequence acting in conjunction with the sugar. If they move both together they can transfer the ERAD-targeting signal, independent of the rest of the protein. Remarkably, the glycosylation sites identified by Spear and Ng do not appear to have a function in the correctly folded protein, suggesting that they evolved for the purpose of targeting the protein for degradation when it misfolds.

Rabiya S. Tuma

rabiya{at}nasw.org

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

Related Article

Single, context-specific glycans can target misfolded glycoproteins for ER-associated degradation

Eric D. Spear and Davis T.W. Ng
J. Cell Biol. 2005 169: 73-82. [Abstract] [Full Text] [PDF]

This Article Full Text (PDF, 506K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Tuma, R. S. Search for Related Content PubMed Articles by Tuma, R. S. Related Collections Related Article Social Bookmarking                            What's this?