gp78: a multifaceted ubiquitin ligase that integrates a unique protein degradation pathway from the endoplasmic reticulum.
The endoplasmic reticulum (ER) is the site for maturation of proteins destined for the secretory pathway. Failure in maturation leads to production of misfolded proteins that are eliminated through the ER-associated degradation (ERAD) pathway. ERAD is a complex process that includes misfolded protein recognition, retrotranslocation to the cytosol, ubiquitination and proteasomal degradation. gp78 is an E3 ubiquitin ligase that integrates these ERAD steps by nucleating a unique degradation machine, which uses the p97/VCP-Npl4 complex for retrotranslocation instead of the wellknown p97/VCP-Ufd1-Npl4 complex. A growing list of substrates have been identified for gp78, which highlights the importance of gp78-mediated ERAD in essential physiological pathways and pathological processes.
Center for Biomedical Engineering and Technology, Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Zhiliang
Z
Chen
Shaojun
S
Du
Shengyun
S
Fang
D000595:Amino Acid Sequence; D000818:Animals; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D019636:Neurodegenerative Diseases / Q000378:metabolism; D059748:Proteolysis; D060285:Receptors, Autocrine Motility Factor / Q000737:chemistry* / Q000378:metabolism*; D016415:Sequence Alignment; D015398:Signal Transduction; D054875:Ubiquitination
C555000:AMFR protein, human; D060285:Receptors, Autocrine Motility Factor