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-δ, a well-characterized ERAD substrate. In contrast, gp78 lacking an intact RING finger or its multiple membrane-spanning domains stabilizes CD3-δ. 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.
Bibliography
Fang, S., Ferrone, M., Yang, C., Jensen, J. P., Tiwari, S., & Weissman, A. M. (2001). The tumor autocrine motility factor receptor, gp78, is a ubiquitin protein ligase implicated in degradation from the endoplasmic reticulum. Proceedings of the National Academy of Sciences, 98(25), 14422â14427.
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Dates
Type | When |
---|---|
Created | 23 years ago (July 26, 2002, 10:35 a.m.) |
Deposited | 3 years, 4 months ago (April 13, 2022, 9:49 a.m.) |
Indexed | 2 days, 22 hours ago (Aug. 19, 2025, 6:22 a.m.) |
Issued | 23 years, 8 months ago (Nov. 27, 2001) |
Published | 23 years, 8 months ago (Nov. 27, 2001) |
Published Online | 23 years, 8 months ago (Nov. 27, 2001) |
Published Print | 23 years, 8 months ago (Dec. 4, 2001) |
@article{Fang_2001, title={The tumor autocrine motility factor receptor, gp78, is a ubiquitin protein ligase implicated in degradation from the endoplasmic reticulum}, volume={98}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.251401598}, DOI={10.1073/pnas.251401598}, number={25}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Fang, Shengyun and Ferrone, Marco and Yang, Cuihong and Jensen, Jane P. and Tiwari, Swati and Weissman, Allan M.}, year={2001}, month=nov, pages={14422–14427} }