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: Gad Asher, Yosef Shaul
• Journal: Cell cycle (Georgetown, Tex.) (Cell Cycle) Vol. 4 Issue 8 Pg. 1015-8 (Aug 2005) ISSN: 1551-4005 [Electronic] United States
• PMID: 16082197 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Nuclear Proteins
• Tumor Suppressor Protein p53
• Ubiquitin
• NAD
• NADP
• NAD(P)H Dehydrogenase (Quinone)
• NQO1 protein, human
• UBE3A protein, human
• Ubiquitin-Protein Ligases
• Proteasome Endopeptidase Complex
• ATP dependent 26S protease

Topics

• Cell Line, Tumor
• Feedback, Physiological
• Gene Expression Regulation, Enzymologic
• Genes, p53
• Humans
• Models, Biological
• Models, Molecular
• NAD (chemistry)
• NAD(P)H Dehydrogenase (Quinone) (chemistry)
• NADP (metabolism)
• Nuclear Proteins (chemistry)
• Proteasome Endopeptidase Complex (chemistry, metabolism)
• Protein Conformation
• Tumor Suppressor Protein p53 (metabolism, physiology)
• Ubiquitin (chemistry)
• Ubiquitin-Protein Ligases (chemistry, metabolism)