dc.contributor.author | Greenblatt, Wesley H. | |
dc.contributor.author | Rubenstein, Eric M. | |
dc.contributor.author | Kreft, Stefan G. | |
dc.contributor.author | Swanson, Robert | |
dc.contributor.author | Hochstrasser, Mark | |
dc.date.accessioned | 2012-11-16T20:11:38Z | |
dc.date.available | 2012-11-16T20:11:38Z | |
dc.date.issued | 2012-06 | |
dc.date.submitted | 2012-03 | |
dc.identifier.issn | 0021-9525 | |
dc.identifier.issn | 1540-8140 | |
dc.identifier.uri | http://hdl.handle.net/1721.1/74669 | |
dc.description.abstract | Little is known about quality control of proteins that aberrantly or persistently engage the endoplasmic reticulum (ER)-localized translocon en route to membrane localization or the secretory pathway. Hrd1 and Doa10, the primary ubiquitin ligases that function in ER-associated degradation (ERAD) in yeast, target distinct subsets of misfolded or otherwise abnormal proteins based primarily on degradation signal (degron) location. We report the surprising observation that fusing Deg1, a cytoplasmic degron normally recognized by Doa10, to the Sec62 membrane protein rendered the protein a Hrd1 substrate. Hrd1-dependent degradation occurred when Deg1-Sec62 aberrantly engaged the Sec61 translocon channel and underwent topological rearrangement. Mutations that prevent translocon engagement caused a reversion to Doa10-dependent degradation. Similarly, a variant of apolipoprotein B, a protein known to be cotranslocationally targeted for proteasomal degradation, was also a Hrd1 substrate. Hrd1 therefore likely plays a general role in targeting proteins that persistently associate with and potentially obstruct the translocon. | en_US |
dc.language.iso | en_US | |
dc.publisher | Rockefeller University Press, The | en_US |
dc.relation.isversionof | http://dx.doi.org/10.1083/jcb.201203061 | en_US |
dc.rights | Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/3.0/ | en_US |
dc.source | Rockefeller UP | en_US |
dc.title | Aberrant substrate engagement of the ER translocon triggers degradation by the Hrd1 ubiquitin ligase | en_US |
dc.type | Article | en_US |
dc.identifier.citation | Rubenstein, E. M. et al. “Aberrant Substrate Engagement of the ER Translocon Triggers Degradation by the Hrd1 Ubiquitin Ligase.” The Journal of Cell Biology 197.6 (2012): 761–773. © 2012 by The Rockefeller University Press | en_US |
dc.contributor.department | Harvard University--MIT Division of Health Sciences and Technology | en_US |
dc.contributor.mitauthor | Greenblatt, Wesley H. | |
dc.relation.journal | Journal of Cell Biology | en_US |
dc.eprint.version | Final published version | en_US |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | en_US |
eprint.status | http://purl.org/eprint/status/PeerReviewed | en_US |
dspace.orderedauthors | Rubenstein, E. M.; Kreft, S. G.; Greenblatt, W.; Swanson, R.; Hochstrasser, M. | en |
mit.license | PUBLISHER_CC | en_US |
mit.metadata.status | Complete | |