A role for mammalian Ubc6 homologues in ER-associated protein degradation

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Item Type:	Article
Title:	A role for mammalian Ubc6 homologues in ER-associated protein degradation
Creators Name:	Lenk, U., Yu, H., Walter, J., Gelman, M.S., Hartmann, E., Kopito, R.R. and Sommer, T.
Abstract:	Integral membrane and secretory proteins which fail to fold productively are retained in the endoplasmic reticulum and targeted for degradation by cytoplasmic proteasomes. Genetic and biochemical analyses suggest that substrates of this pathway must be dislocated across the membrane of the endoplasmic reticulum (ER) by a process requiring a functional Sec61 complex and multiubiquitinylation. In yeast, the tail-anchored ubiquitin-conjugating enzyme Ubc6p, which is localized to the cytoplasmic surface of the ER, participates in ER-associated degradation (ERAD) of misfolded proteins. Here we describe the identification of two families of mammalian Ubc6p-related proteins. Members of both families are also located in the ER membrane and display a similar membrane topology as the yeast enzyme. Furthermore we show that expression of elevated levels of wild-type and dominant-negative alleles of these components affects specifically ERAD of the α subunit of the T-cell receptor and a mutant form of the CFTR protein. Similarly, we describe that the expression level of Ubc6p in yeast is also critical for ERAD, suggesting that the Ubc6p function is highly conserved from yeast to mammals.
Keywords:	Endoplasmic Reticulum, Proteolysis, Ubiquitin, Animals
Source:	Journal of Cell Science
ISSN:	0021-9533
Publisher:	Company of Biologists
Volume:	115
Number:	14
Page Range:	3007-3014
Date:	1 January 2002
Official Publication:	http://jcs.biologists.org/cgi/content/abstract/115/14/3007
PubMed:	View item in PubMed

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