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 cerebellum, hippocampus, and olfactory bulb. 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 transformation. P311 mRNA expression was decreased sharply in both neural and smooth muscle cells when the cells were transformed by coexpression of the oncogenic tyrosine kinase receptor Met and its ligand hepatocyte growth factor/scatter factor. The P311 mRNA was found to encode an 8-kDa polypeptide that was subject to rapid degradation by the lactacystin-sensitive ubiquitin/proteasome system and an unidentified metalloprotease, resulting in a protein half-life of about 5 min. These data suggest that P311 expression is dramatically decreased by several pathways that regulate cellular growth.
Taylor
G A
GA
Advanced Bioscience Laboratories Basic Research Program, NCI-Frederick Cancer Research and Development Center, Frederick, Maryland 21702, USA.
Hudson
E
E
Resau
J H
JH
Vande Woude
G F
GF
D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001921:Brain; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000235:genetics; D002460:Cell Line; D017690:Cell Transplantation; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000187:drug effects; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009097:Multienzyme Complexes / Q000378:metabolism*; D009130:Muscle, Smooth; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D010618:Phenanthrolines / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex; D012333:RNA, Messenger / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D014170:Transformation, Genetic; D014452:Ubiquitins / Q000378:metabolism*
D009097:Multienzyme Complexes; D009419:Nerve Tissue Proteins; D010618:Phenanthrolines; D012333:RNA, Messenger; D014452:Ubiquitins; C067713:lactacystin; D017228:Hepatocyte Growth Factor; D020794:Receptor Protein-Tyrosine Kinases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; C025205:1,10-phenanthroline; D000111:Acetylcysteine