Transcriptional Regulation by P53

Beckerman, Rachel; Prives, Carol

doi:10.1101/cshperspect.a000935

Cited by 486 publications

(464 citation statements)

References 178 publications

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“…p53 acts as tetrameric transcription factor, which controls the expression of a large set of genes involved in significant cellular processes including DNA damage detection, cell cycle arrest, apoptosis, DNA repair, and senescence [134]. It is both involved in intrinsic and extrinsic pathways of apoptosis by inducing transcription of several proteins like PUMA, Bid, Bax, TRAILR2, and CD95, which is called transcriptiondependent apoptotic pathway of p53 taking place in the nucleus [138]. In this pathway of p53-dependent apoptosis, the trans-activation domain of p53 interacts with the players of basal transcription machinery such as the transcriptional coactivator p300/CBP [139].…”

Section: Death Receptormentioning

confidence: 99%

Major apoptotic mechanisms and genes involved in apoptosis

et al. 2016

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As much as the cellular viability is important for the living organisms, the elimination of unnecessary or damaged cells has the opposite necessity for the maintenance of homeostasis in tissues, organs and the whole organism. Apoptosis, a type of cell death mechanism, is controlled by the interactions between several molecules and responsible for the elimination of unwanted cells from the body. Apoptosis can be triggered by intrinsically or extrinsically through death signals from the outside of the cell. Any abnormality in apoptosis process can cause various types of diseases from cancer to auto-immune diseases. Different gene families such as caspases, inhibitor of apoptosis proteins, B cell lymphoma (Bcl)-2 family of genes, tumor necrosis factor (TNF) receptor gene superfamily, or p53 gene are involved and/or collaborate in the process of apoptosis. In this review, we discuss the basic features of apoptosis and have focused on the gene families playing critical roles, activation/inactivation mechanisms, upstream/downstream effectors, and signaling pathways in apoptosis on the basis of cancer studies. In addition, novel apoptotic players such as miRNAs and sphingolipid family members in various kind of cancer are discussed.

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Section: Death Receptormentioning

confidence: 99%

Major apoptotic mechanisms and genes involved in apoptosis

et al. 2016

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“…Although this was quite an unexpected finding, in retrospect this observation fits well within the cell-autonomous function of TP53. Indeed, upon DNA damage, TP53 activates the appropriate target genes to either repair the damage or launch the apoptotic program (Beckerman and Prives 2010). Although we now have a better understanding of the TP53 cistrome, it remains to be discovered how generic activation of the same set of enhancers is differentially steered in the currently operational gene regulatory network, and how the cellular context further contributes to the resulting responses like apoptosis or growth arrest.…”

Section: Tp53 Enhancer Logicmentioning

confidence: 99%

Multiplex enhancer-reporter assays uncover unsophisticated TP53 enhancer logic

et al. 2016

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Transcription factors regulate their target genes by binding to regulatory regions in the genome. Although the binding preferences of TP53 are known, it remains unclear what distinguishes functional enhancers from nonfunctional binding. In addition, the genome is scattered with recognition sequences that remain unoccupied. Using two complementary techniques of multiplex enhancer-reporter assays, we discovered that functional enhancers could be discriminated from nonfunctional binding events by the occurrence of a single TP53 canonical motif. By combining machine learning with a meta-analysis of TP53 ChIP-seq data sets, we identified a core set of more than 1000 responsive enhancers in the human genome. This TP53 cistrome is invariably used between cell types and experimental conditions, whereas differences among experiments can be attributed to indirect nonfunctional binding events. Our data suggest that TP53 enhancers represent a class of unsophisticated cell-autonomous enhancers containing a single TP53 binding site, distinct from complex developmental enhancers that integrate signals from multiple transcription factors.

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“…Following DNA damage, ATM (ataxia-telangiectasia mutated)-mediated phosphorylation leads to destabilization of Mdm2, therefore triggering p53 stabilization and activation (Maya et al, 2001). Once activated, p53 induces expression of a large number of genes including Siva-1 and Mdm2 that regulates apoptosis and cell cycle progression (Beckerman and Prives, 2010). Intriguingly, our recent data reveals an important role of Siva-1 as an adaptor for Mdm2 to inhibit p53 (Du et al, 2009).…”

Section: An Auto-regulatory Feedback Loop Of P53-siva-1mentioning

confidence: 73%

Multifaceted functions of Siva-1: more than an Indian God of Destruction

2012

Protein Cell

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Siva-1, as a p53-inducible gene, has been shown to induce extensive apoptosis in a number of different cell lines. Recent evidence suggests that Siva-1 functions as a part of the auto-regulatory feedback loop that restrains p53 through facilitating Mdm2-mediated p53 degradation. Also, Siva-1 plays an important role in suppressing tumor metastasis. Here we review the current understanding of Siva-1-mediated apoptotic signaling pathway. We also add comments on the p53-Siva-1 feedback loop, the novel function of Siva-1 in suppressing tumor metastasis, and their potential implications.

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Transcriptional Regulation by P53

Cited by 486 publications

References 178 publications

Major apoptotic mechanisms and genes involved in apoptosis

Major apoptotic mechanisms and genes involved in apoptosis

Multiplex enhancer-reporter assays uncover unsophisticated TP53 enhancer logic

Multifaceted functions of Siva-1: more than an Indian God of Destruction

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