title: The tumor autocrine motility factor receptor, gp78, is a ubiquitin protein ligase implicated in degradation from the endoplasmic reticulum.
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.
authors.affiliation: Regulation of Protein Function Laboratory, Center for Cancer Research, National Cancer Institute, Building 10, Room 1B34, 9000 Rockville Pike, Bethesda, MD 20892-1152, USA.
authors.forename: S
authors.initials: S
authors.lastname: Fang
authors.forename: M
authors.initials: M
authors.lastname: Ferrone
authors.forename: C
authors.initials: C
authors.lastname: Yang
authors.forename: J P
authors.initials: JP
authors.lastname: Jensen
authors.forename: S
authors.initials: S
authors.lastname: Tiwari
authors.forename: A M
authors.initials: AM
authors.lastname: Weissman
mesh_terms: D000818:Animals; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006801:Humans; D008025:Ligases / Q000235:genetics / Q000378:metabolism*; D060285:Receptors, Autocrine Motility Factor; D018121:Receptors, Cytokine / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D025801:Ubiquitin / Q000378:metabolism; D044763:Ubiquitin-Conjugating Enzymes; D044767:Ubiquitin-Protein Ligases
chemical_list: D018121:Receptors, Cytokine; D011994:Recombinant Proteins; D025801:Ubiquitin; C079437:UBE2L3 protein, human; D044763:Ubiquitin-Conjugating Enzymes; C555000:AMFR protein, human; D060285:Receptors, Autocrine Motility Factor; D044767:Ubiquitin-Protein Ligases; D008025:Ligases