p53 vs. ISG15: Stop, you’re killing me
- National Inst. of Environmental Health Sciences, Research Triangle Park, NC (United States). Lab. of Molecular Genetics. Chromosome Stability Selction
- National Inst. of Environmental Health Sciences, Research Triangle Park, NC (United States). Lab. of Molecular Genetics. Chromosome Stability Selction; Brookhaven National Lab. (BNL), Upton, NY (United States). Biosciences Dept.
The stability of the p53 tumor-suppressing transcription factor is tightly regulated. In normal, unstressed cells, p53 is kept at low levels primarily by its major negative regulator MDM2 through polyubiquitylation at several N- and/or C-terminal sites, thus targeting p53 for degradation through the 26S proteasome. Under certain conditions, MDM2 also may monoubiquitylate or neddylate p53, but these primarily serve different functions. p53 also can be ubiquitylated by several other E3 ligases, but at least in the cells and tissues that have been examined, MDM2 is the major regulator of p53 stability.1 Both MDM2 and MDMX also block the activity of p53 as a transcription factor by binding the N-terminal transactivating domains. In contrast, many tumor-derived mutant p53s are much more stable and accumulate to high levels in tumor cells, although generally the ability of these mutants to act as a transcription factor is impaired. Both wildtype and mutant p53s also are covalently posttranslationally modified at many sites in a variety of different ways, including phosphorylation of serines and threonines and acetylation or methylation of lysines.
- Research Organization:
- Brookhaven National Laboratory (BNL), Upton, NY (United States)
- Sponsoring Organization:
- USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division
- OSTI ID:
- 1629165
- Journal Information:
- Cell Cycle (Georgetown, Tex), Vol. 13, Issue 14; ISSN 1538-4101
- Publisher:
- Taylor and FrancisCopyright Statement
- Country of Publication:
- United States
- Language:
- English
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