Regulation of P311 expression by Met-hepatocyte growth factor/scatter factor and the ubiquitin/proteasome system

P311 is a mouse cDNA originally identified for its high expression in late- stage embryonic brain and adult cer ebellum, hippocampus, and olfactory bul b. The protein product of P311, however, had not been identified previously , and its function remains unknown. We report here that P311 expression is regulated at multiple levels by pathways that control cellular transformati on. P311 mRNA expression was decreased sharply in both neural and smooth mu scle cells when the cells were transformed by coexpression of the oncogenic tyrosine kinase receptor Met and its ligand hepatocyte growth factor/scatt er factor. The P311 mRNA was found to encode an 8-kDa polypeptide that was subject to rapid degradation by the lactacystin-sensitive ubiquitin/proteas ome system and an unidentified metalloprotease, resulting in a protein half -life of about 5 min. These data suggest that P311 expression is dramatical ly decreased by several pathways that regulate cellular growth.