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An integrated view of p53 dynamics, function, and reactivation.

ABSTRACT: The tumor suppressor p53 plays a vital role in responding to cell stressors such as DNA damage, hypoxia, and tumor formation by inducing cell-cycle arrest, senescence, or apoptosis. Expression level alterations and mutational frequency implicates p53 in most human cancers. In this review, we show how both computational and experimental methods have been used to provide an integrated view of p53 dynamics, function, and reactivation potential. We argue that p53 serves as an exceptional case study for developing methods in modeling intrinsically disordered proteins. We describe how these methods can be leveraged to improve p53 reactivation molecule design and other novel therapeutic modalities, such as PROteolysis TARgeting Chimeras (PROTACs).

SUBMITTER: Demir O

PROVIDER: S-EPMC8985518 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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An integrated view of p53 dynamics, function, and reactivation.

Demir Özlem Ö Barros Emilia P EP Offutt Tavina L TL Rosenfeld Mia M Amaro Rommie E RE

Current opinion in structural biology 20210102

The tumor suppressor p53 plays a vital role in responding to cell stressors such as DNA damage, hypoxia, and tumor formation by inducing cell-cycle arrest, senescence, or apoptosis. Expression level alterations and mutational frequency implicates p53 in most human cancers. In this review, we show how both computational and experimental methods have been used to provide an integrated view of p53 dynamics, function, and reactivation potential. We argue that p53 serves as an exceptional case study ...[more]

PMID: 33401096

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