title: p53 proteasomal degradation: poly-ubiquitination is not the whole story.
abstract: Protein degradation is a key cellular process involved in almost every aspect of the living cell. The current prevailing concept is that proteins are stable unless marked by poly-ubiquitination for degradation by the proteasomes. Studies on the tumor suppressor p53 have indeed demonstrated that poly-ubiquitination of p53 by different E3 ubiquin ligases targets p53 for degradation by the 26S proteasomes. Recent findings suggest that p53 also undergoes ubiquitin-independent degradation by the 20S proteasomes and that this process is regulated by NAD(P)H quinone oxidoreductase 1 (NQO1) together with NADH. This "degradation by default" mechanism sheds new light on our understanding of p53 degradation and possibly on protein degradation in general and may establish a new principle in protein stability with wide physiological implications.
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Gad
authors.initials: G
authors.lastname: Asher
authors.forename: Yosef
authors.initials: Y
authors.lastname: Shaul
mesh_terms: D045744:Cell Line, Tumor; D025461:Feedback, Physiological; D015971:Gene Expression Regulation, Enzymologic; D016158:Genes, p53; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D009243:NAD / Q000737:chemistry; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000737:chemistry; D009249:NADP / Q000378:metabolism; D009687:Nuclear Proteins / Q000737:chemistry; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism / Q000502:physiology*; D025801:Ubiquitin / Q000737:chemistry*; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry* / Q000378:metabolism
chemical_list: D009687:Nuclear Proteins; D016159:Tumor Suppressor Protein p53; D025801:Ubiquitin; D009243:NAD; D009249:NADP; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; C471639:UBE3A protein, human; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease