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

gp78, also known as the tumor autocrine motility factor receptor, is a tran smembrane 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 specificall y recruits MmUBC7, a ubiquitin-conjugating enzyme (E2) implicated in ER-ass ociated degradation (ERAD), through a region distinct from the RING finger. gp78 can target itself for proteasomal degradation in a RING finger- and M mUBC7-dependent manner. Importantly, gp78 can also mediate degradation of C D3-delta, a well-characterized ERAD substrate. In contrast, gp78 lacking an intact RING finger or its multiple membrane-spanning domains stabilizes CD 3-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.