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Proc Natl Acad Sci U S A. 2001 Dec 4;98(25):14422-7. Epub 2001 Nov 27.

The tumor autocrine motility factor receptor, gp78, is a ubiquitin protein ligase implicated in degradation from the endoplasmic reticulum.

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  • 1Regulation of Protein Function Laboratory, Center for Cancer Research, National Cancer Institute, Building 10, Room 1B34, 9000 Rockville Pike, Bethesda, MD 20892-1152, USA.

Abstract

gp78, also known as the tumor autocrine motility factor receptor, is a transmembrane protein whose expression is correlated with tumor metastasis. We establish that gp78 is a RING finger-dependent ubiquitin protein ligase (E3) of the endoplasmic reticulum (ER). Consistent with this, gp78 specifically recruits MmUBC7, a ubiquitin-conjugating enzyme (E2) implicated in ER-associated degradation (ERAD), through a region distinct from the RING finger. gp78 can target itself for proteasomal degradation in a RING finger- and MmUBC7-dependent manner. Importantly, gp78 can also mediate degradation of CD3-delta, a well-characterized ERAD substrate. In contrast, gp78 lacking an intact RING finger or its multiple membrane-spanning domains stabilizes CD3-delta. gp78 has thus been found to be an example of a mammalian cellular E3 intrinsic to the ER, suggesting a potential link between ubiquitylation, ERAD, and metastasis.

PMID:
11724934
[PubMed - indexed for MEDLINE]
PMCID:
PMC64697
Free PMC Article
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