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• W4240593337 abstract "Inactivation of the p53 tumor suppressor pathway is essential for the development of most or all human cancers. Over 50% of cancers harbor missense mutations in p53 that destroy its normal function.1 In cancers that retain wild-type p53, the protein is often inactivated through other means, including being abnormally sequestered in the cytoplasm, over-expression of MDM2 (the key negative regulator of p53), and deletion of p14/Arf (which normally inhibits MDM2 function). P53 undergoes nuclear-cytoplasmic shuttling and, in most unstressed cells, is expressed at low levels localized in both the nucleus and the cytoplasm. In response to DNA damage and other stresses, p53 is subject to various post-translational modifications that result in its stabilization, accumulation in the nucleus, and activation as a transcription factor. While most p53 accumulates in the nucleus following stress, recent studies indicate a significant fraction remains in the cytoplasm, and that both nuclear and cytoplasmic p53 participate in its tumor suppressor program.2 Notably, certain post-translational modifications may direct p53 to specific sub-cellular locales (Table 1), and this appear to be important in unleashing p53’s full growth suppressive capabilities. For example, at least some nuclear p53 that accumulates following certain stresses is directed to sub-nuclear domains (PML bodies) where it is subjected to further activating modifications. Similarly, cytoplasmic p53 is directed to the mitochondria following stress where it interacts with pro- and anti-apoptotic members of the Bcl2 family, resulting in the release of factors from the mitochondria that drive apoptosis. This chapter will review studies of p53 localization control including its nuclear-cytoplasmic shuttling, movement to PML bodies and to the mitochondria." @default.
• W4240593337 created "2022-05-12" @default.
• W4240593337 creator A5074352836 @default.
• W4240593337 date "2010-01-01" @default.
• W4240593337 modified "2023-09-24" @default.
• W4240593337 title "p53 Localization" @default.
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• W4240593337 doi "https://doi.org/10.1007/978-1-4419-8231-5_8" @default.
• W4240593337 hasPublicationYear "2010" @default.
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