Awakening the “guardian of genome”: reactivation of mutant p53

Binayke, Akshay; Mishra, Sarthak; Suman, Prabhat; Das, Suman; Chander, Harish

doi:10.1007/s00280-018-3701-x

Cited by 39 publications

(27 citation statements)

References 87 publications

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“…Transcription factor p53 is considered to regulate cell cycle and inhibit cell carcinogenesis [31]. However, the mutation of p53 not only loses the function of tumor suppressor but also regains the function of oncogene to promote malignant transformation of cells [32]. Among several noncanonical cell deaths, including apoptosis, ferroptosis, necroptosis, and paraptosis, p53 is the most important regulator to switch these cell deaths [10].…”

Section: Discussionmentioning

confidence: 99%

Transcription Factor p53 Suppresses Tumor Growth by Prompting Pyroptosis in Non-Small-Cell Lung Cancer

Zhang

Zhu

et al. 2019

Oxidative Medicine and Cellular Longevity

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Objective To evaluate the effect of p53 on pyroptosis and its inhibitory role on tumor growth in non-small-cell lung cancer (NSCLC). Methods The correlation of p53 and pyroptosis was determined in tumor tissues of NSCLC patients. The pyroptotic level was detected in A549 cells to clarify the effect of p53 on pyroptosis. p53 overexpression A549 tumor-bearing mice were used to clarify the therapeutic target of p53 in NSCLC treatment. Results p53 expression level was positively related to pyroptosis in NSCLC tissues. In in vitro assays, p53 directly regulated pyroptosis in A549 cells. p53-specific knockdown blocked lipopolysaccharide- (LPS-) induced pyroptosis. In in vivo assays, p53 overexpression in A549 markedly decreased tumor growth and death rate by increasing the pyroptotic level. Conclusions Upregulation of p53 prompts pyroptosis to produce anti-NSCLC effects suggesting the potential of p53 on suppressing tumor growth in NSCLC patients.

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Section: Discussionmentioning

confidence: 99%

Transcription Factor p53 Suppresses Tumor Growth by Prompting Pyroptosis in Non-Small-Cell Lung Cancer

Zhang

Zhu

et al. 2019

Oxidative Medicine and Cellular Longevity

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“…Indirect support for this hypothesis comes from observation that peptides isolated from phage display libraries are able to bind human and murine p53 (87). It can be speculated that interaction between gp53 and p53 may restore transcriptional activity of mutant p53; this could be a promising strategy to harness the potential of p53 in protecting cells from carcinogenesis through cell-cycle arrest, senescence, and apoptosis (88).…”

Section: Discussionmentioning

confidence: 99%

Phage composition of a fermented milk and colostrum product assessed by microbiome array; putative role of open reading frames in reference to cell signaling and neurological development

Pacini¹,

Ruggiero²

2019

Preprint

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Bacteriophages (phages), Earth's most numerous biological entities, are natural constituents of alimentary matrices; in this study we describe the characterization of phage populations in a product obtained by fermentation of bovine milk and colostrum. Such characterizations were achieved using a microarray consisting of a chip covered in short DNA sequences that are specific to certain target organisms for a total of approximately 12,000 species. The only viruses evidenced by the array belonged to Siphoviridae, the largest phage family that targets bacteria and archea. The array yielded 27 iterations corresponding to a unique target. We discuss the putative role of some open reading frames of these phages in conferring health-supporting properties.

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“…The denaturation of mutp53 at physiological temperature largely contributes to the inabilily of mutp53 to activate downstream tumor suppressive genes. Therefore, several mutp53 reactivating peptides, such as CDB3, peptide-46 and pCAPs, have been identified to restore wildtype p53 activities to cancer cells (123,124). On the other hand, a large portion of p53 mutants have been reported to form protein aggregates, which contributes to the GOF properties that promote tumor growth.…”

Section: Small Peptidesmentioning

confidence: 99%

Mutant p53 in Cancer Progression and Targeted Therapies

et al. 2020

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TP53 is the most frequently mutated tumor suppressor gene in human cancer. The majority of mutations of p53 are missense mutations, leading to the expression of the full length p53 mutant proteins. Mutant p53 (Mutp53) proteins not only lose wild-type p53dependent tumor suppressive functions, but also frequently acquire oncogenic gain-offunctions (GOF) that promote tumorigenesis. In this review, we summarize the recent advances in our understanding of the oncogenic GOF of mutp53 and the potential therapies targeting mutp53 in human cancers. In particular, we discuss the promising drugs that are currently under clinical trials as well as the emerging therapeutic strategies, including CRISPR/Cas9 based genome edition of mutant TP53 allele, small peptide mediated restoration of wild-type p53 function, and immunotherapies that directly eliminate mutp53 expressing tumor cells.

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Awakening the “guardian of genome”: reactivation of mutant p53

Cited by 39 publications

References 87 publications

Transcription Factor p53 Suppresses Tumor Growth by Prompting Pyroptosis in Non-Small-Cell Lung Cancer

Transcription Factor p53 Suppresses Tumor Growth by Prompting Pyroptosis in Non-Small-Cell Lung Cancer

Phage composition of a fermented milk and colostrum product assessed by microbiome array; putative role of open reading frames in reference to cell signaling and neurological development

Mutant p53 in Cancer Progression and Targeted Therapies

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