Ubiquitin-independent p53 proteasomal degradation.
The mechanism of p53 proteasomal degradation through polyubiquitination is well characterized. The basic assumption behind this mechanism is that p53 is inherently stable unless sensitized to degradation by polyubiquitination. However, a number of studies provide evidence for p53 to be naturally unstable. Consistent with this attribute is the fact that both p53 N- and C-termini are intrinsically unstructured. Recent findings provide evidence for p53 to be degraded by the 20S proteasome by default unless it escapes this process. A number of mechanisms were demonstrated and proposed to play a role in rescuing p53 from default degradation. These mechanisms, their biological implications, and relevance to cancer are reviewed in this article.
Tsvetkov
P
P
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
Reuven
N
N
Shaul
Y
Y
D006801:Humans; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism*
D016159:Tumor Suppressor Protein p53; D025801:Ubiquitin; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; D046988:Proteasome Endopeptidase Complex