Novel characterization of a G-protein coupled receptor, Autocrine Motility Factor Receptor (AMFR): an endoplasmic reticulum-localized E3 ubiquitin ligase

The endoplasmic reticulum is a membrane network within cells involved in the synthesis, modification, and transport of cellular materials. Endoplasmic Reticulum Associated Protein Degradation (ERAD) is a cellular process that identifies unneeded or misfolded proteins of the endoplasmic reticulum and modifies the protein by attaching to it a ubiquitin protein. This ubiquitination process serves to mark the protein for destruction – a key process that helps prevent a range of diseases. Autocrine motility factor receptor (AMFR) is a transmembrane protein expressed on the cell surface and in a smooth subdomain of the endoplasmic reticulum (SER). AMFR has a critical function in the ubiquitination process, binding to the regulatory protein autocrine motility factor (AMF). Overexpression of AMF and AMFR occurs in a number of malignancies and participates in cancer cell migration during cancer progression and metastasis. It has been observed that AMF is secreted by tumour cells and acts as a protein messenger to other cells. However, its mechanisms remain unknown. Maria Abramow-Newerly is determining the signalling pathways used by AFMR following its binding to AMF, working to identify critical proteins and factors that may all tightly regulate AMFR expression and distribution within normal and cancer cell lines. In particular, she is focusing on characterizing AMFR as a G-protein coupled receptor, a family of proteins that serve as important drug targets for a number of diseases. Abramow-Newerly’s studies may contribute to the future design of drugs that specifically target components in the AMFR-signalling pathway to reduce cancer cell migration and metastasis