Ubiquitin, E6-AP, and their role in p53 inactivation.
Inactivation of the tumor suppressor protein p53 plays a key role in human carcinogenesis. Activation of the growth-suppressive properties of p53 by appropriate stress signals, including genotoxic stress, is generally accompanied by intracellular accumulation of the protein. This suggests that stabilization of the otherwise short-lived protein is an intrinsic feature of p53 activation. The ubiquitin/proteasome system is believed to be a major proteolytic system involved in selective degradation of cell regulatory proteins. In this review, the potential role of the ubiquitin/proteasome system in p53 degradation and possible mechanisms involved in p53 stability regulation are discussed.
Deutsches Krebsforschungszentrum, Angewandte Tumorvirologie, Heidelberg, Germany.
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Scheffner
D003546:Cysteine Endopeptidases / Q000378:metabolism; D006801:Humans; D008025:Ligases / Q000502:physiology*; D009097:Multienzyme Complexes / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism / Q000502:physiology*; D044767:Ubiquitin-Protein Ligases; D014452:Ubiquitins / Q000502:physiology*
D009097:Multienzyme Complexes; D016159:Tumor Suppressor Protein p53; D014452:Ubiquitins; D044767:Ubiquitin-Protein Ligases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D008025:Ligases