AMFR Antibody #9590

Autocrine motility factor receptor (AMFR/gp78) is a putative seven transmembrane domain G protein-coupled receptor that functions, in part, at the cell surface as a cytokine receptor for autocrine motility factor/phosphoglucose isomerase (AMF/PGI). AMFR is also localized to an intracellular mitochondria-associated smooth ER domain where it functions as an E3 ubiquitin ligase (1). AMFR function, as both a cytokine receptor and ubiquitin ligase, is linked to a variety of cellular signaling cascades associated with metastasis development and increased invasiveness. AMFR was initially proposed to be a RING-H2 E3 ubiquitin ligase after sequence analysis identified a catalytic RING finger and CUE motif, which are responsible for ubiquitin ligase activity and ubiquitin binding, respectively (2,3). Indeed, AMFR is a key component and amongst the best characterized ubiquitin ligases of the endoplasmic reticulum associated degradation (ERAD) machinery, a process involving recognition of misfolded proteins, ubiquitination, deglycosylation, retro-translocation to the cytosol, and targeting to the proteasome (4). Recent studies have shown that AMFR plays an important role in cholesterol homeostasis via the sterol-mediated ubiquitination of HMG-CoA reductase and its cofactor Insig-1 (5,6). Furthermore, AMFR has been implicated in the degradation of apolipoprotein B100 (7). It was recently reported that AMFR degrades the metastasis suppressor KAI-1/CD-82, representing the first evidence that AMFR ubiquitin ligase activity is involved in metastasis development (8). Increased expression of AMFR correlates with a high incidence of recurrence and reduced survival in patients with bladder, colorectal, and gastric cancers (9-11).