Proteolytic degradation of the retinoblastoma family protein p107: A putative cooperative role of calpain and proteasome.
p107 protein, a member of the retinoblastoma family protein, suppresses growth promotion in cancer cells. We have already reported evidence that calpain, a calcium dependent protease is involved in the cleavage of p107 protein. We show here that p107 protein can also be a substrate for ubiquitination. A negative growth regulator, the HMG-CoA reductase inhibitor lovastatin was found to induce loss of p107 protein which was reversible by a specific protease inhibitor lactacystin as well as calpain inhibitor. Following treatment with lovastatin higher molecular weight ubiquitinated forms of p107 were detected by anti-p107 immunoprecipitation and anti-ubiquitin Western blotting. These forms further increased when lactacystin was added to culture medium. These results indicate that ubiquitin-proteasome pathway plays a potential role in the degradation as well as calpain. The data presented here suggest a model in which calpain and ubiquitin-proteasome system possibly play a cooperative role in targeting the protein under certain conditions.
Jang
J S
JS
Department of Internal Medicine, Gyeongsang National University College of Medicine, Chinju 660-701, Korea.
Choi
Y H
YH
D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D015153:Blotting, Western; D042846:CDC2-CDC28 Kinases; D002135:Calcium-Binding Proteins / Q000494:pharmacology; D002154:Calpain / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D006801:Humans; D008148:Lovastatin / Q000494:pharmacology; D008297:Male; D009687:Nuclear Proteins / Q000187:drug effects / Q000378:metabolism*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism*; D050720:Retinoblastoma-Like Protein p107; D012512:Sarcoma, Ewing / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D014452:Ubiquitins / Q000378:metabolism*
D000970:Antineoplastic Agents; D002135:Calcium-Binding Proteins; D015853:Cysteine Proteinase Inhibitors; D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen; C493844:RBL1 protein, human; D016160:Retinoblastoma Protein; D050720:Retinoblastoma-Like Protein p107; D014452:Ubiquitins; C067713:lactacystin; C033668:calpastatin; D008148:Lovastatin; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases; D002154:Calpain; D000111:Acetylcysteine