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Review
. 2014 Dec 23;1(3):e969653.
doi: 10.4161/23723548.2014.969653. eCollection 2014 Jul-Sep.

V体育ios版 - p53 regulation upon genotoxic stress: intricacies and complexities

Affiliations
Review

p53 regulation upon genotoxic stress: intricacies and complexities

Rajni Kumari et al. Mol Cell Oncol. .

Abstract

p53, the revered savior of genomic integrity, receives signals from diverse stress sensors and strategizes to maintain cellular homeostasis. However, the predominance of p53 overshadows the fact that this herculean task is no one-man show; rather, there is a huge army of regulators that reign over p53 at various levels to avoid an unnecessary surge in its levels and sculpt it dynamically to favor one cellular outcome over another. This governance starts right at the time of p53 translation, which is gated by proteins that bind to p53 mRNA and keep a stringent check on p53 protein levels. The same effect is also achieved by ubiquitylases and deubiquitylases that fine-tune p53 turnover and miRNAs that modulate p53 levels, adding precision to this entire scheme. In addition, extensive covalent modifications and differential protein interactions allow p53 to trigger a tailor-made response for a given circumstance. To magnify the marvel, these various tiers of regulation operate simultaneously and in various combinations. In this review, we have tried to provide a glimpse into this bewildering labyrinth. We believe that further studies will result in a better understanding of p53 regulation and that new insights will help unravel many aspects of cancer biology. VSports手机版.

Keywords: cancer; genotoxic stress; miRNA; p53; post-translational modifications V体育安卓版. .

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Figures

Figure 1.
Figure 1.
Diverse modes of p53 regulation. The multitude of ways by which p53 can be regulated include regulation at the level of translation and mRNA stability, cellular proteins that bind to and regulate p53 function and stability, and post-translational modifications.
Figure 2.
Figure 2.
Selected modifiers and demodifiers of p53. These modifications act as determinants of p53 levels and p53-mediated cell fate decisions.
Figure 3.
Figure 3.
Various mechanisms by which miRNAs positively and negatively regulate p53 to maintain cellular homeostasis. (a) miR-506 leads to DNA damage via ROS generation and hence activates p53 through the DNA damage pathway. (b) miR-34 positively regulates p53 by inhibiting its deacetylase SIRT1. (c) Various miRNAs negatively regulate p53 through direct base pairing with its 3’UTR. (d) Several miRNAs target MDM2-mediated p53 ubiquitylation: miR-542–3p and miR-29 positively regulate p53 by targeting p53-MDM2 interaction and MDM2, respectively; miR-21 negatively regulates p53 by inhibiting HNRPK, an inhibitor of MDM2, leading to increased MDM2 activity and p53 ubiquitylation.

References (V体育官网)

    1. Okoshi R, Ando K, Suenaga Y, Sang M, Kubo N, Kizaki H, Nakagawara A, Ozaki T. Transcriptional regulation of tumor suppressor p53 by cAMP-responsive element-binding protein/AMP-activated protein kinase complex in response to glucose deprivation. Genes Cells 2009; 14:1429-40; PMID:19930465; "VSports最新版本" http://dx.doi.org/10.1111/j.1365-2443.2009.01359.x - DOI - PubMed
    1. Reisman D, Elkind NB, Roy B, Beamon J, Rotter V. c-Myc trans-activates the p53 promoter through a required downstream CACGTG motif. Cell Growth Differ 1993; 4:57-65; PMID:8494784 - PubMed
    1. Deffie A, Wu H, Reinke V, Lozano G. The tumor suppressor p53 regulates its own transcription. Mol Cell Biol 1993; 13:3415-23; PMID:7684498 - PMC - PubMed
    1. Fu L, Benchimol S. Participation of the human p53 3'UTR in translational repression and activation following gamma-irradiation. EMBO J 1997; 16:4117-25; PMID:9233820; http://dx.doi.org/10.1093/emboj/16.13.4117 - DOI - PMC - PubMed
    1. Mosner J, Mummenbrauer T, Bauer C, Sczakiel G, Grosse F, Deppert W. Negative feedback regulation of wild-type p53 biosynthesis. EMBO J 1995; 14:4442-9; PMID:7556087 - PMC - PubMed

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