title: On the involvement of calpains in the degradation of the tumor suppressor protein p53.
abstract: A crude fraction that contains ubiquitin-protein ligases contains also a proteolytic activity of approximately 100 kDa that cleaves p53 to several fragments. The protease does not require ATP and is inhibited in the crude extract by an endogenous approximately 250 kDa inhibitor. The proteinase can be inhibited by chelating the Ca2+ ions, by specific cysteine proteinase inhibitors and by peptide aldehyde derivatives that inhibit calpains. Purified calpain demonstrates an identical activity that can be inhibited by calpastatin, the specific protein inhibitor of the enzyme. Thus, it appears that the activity we have identified in the extract is catalyzed by calpain. The calpain in the extract degrades also N-myc, c-Fos and c-Jun, but not lysozyme. In crude extract, the calpain activity can be demonstrated only when the molar ratio of the calpain exceeds that of its native inhibitor. Recent experimental evidence implicates both the ubiquitin proteasome pathway and calpain in the degradation of the tumor suppressor, and it was proposed that the two pathways may play a role in targeting the protein under various conditions. The potential role of the two systems in this important metabolic process is discussed.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Technion-Israel Institute of Technology, Haifa.
authors.forename: H
authors.initials: H
authors.lastname: Gonen
authors.forename: D
authors.initials: D
authors.lastname: Shkedy
authors.forename: S
authors.initials: S
authors.lastname: Barnoy
authors.forename: N S
authors.initials: NS
authors.lastname: Kosower
authors.forename: A
authors.initials: A
authors.lastname: Ciechanover
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002154:Calpain / Q000378:metabolism*; D002850:Chromatography, Gel; D015853:Cysteine Proteinase Inhibitors / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D002135:Calcium-Binding Proteins; D015853:Cysteine Proteinase Inhibitors; D016159:Tumor Suppressor Protein p53; C033668:calpastatin; D000255:Adenosine Triphosphate; D002154:Calpain