https://pubmed.ncbi.nlm.nih.gov/31483066/
However, Trp53 R178E tumors exhibit remarkably better chemotherapy responses than Trp53 -/- ones, resulting in enhanced eradication of p53-mutated tumor cells. Together, this provides genetic proof-of-principle evidence that a p53 mutant can be highly tumorigenic and yet retain apoptotic activity which provides a survival benefit in the context

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6129128/
A further analysis of patient cohorts of both the glioma and gastric cancer datasets uncovered a strong association between mutant p53 residual activity and survival in males (P = 0.002 and P = 0.02, respectively) that was not present in the female cohorts (P = 0.16 and P = 0.50, respectively) (Figure 3, C-F).

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6792016/
Engineered p53 mutant mice are valuable tools for delineating p53 functions in tumor suppression and cancer therapy. Here, we have introduced the R178E mutation into the Trp53 gene of mice to specifically ablate the cooperative nature of p53 DNA binding. Trp53 R178E mice show no detectable target gene regulation and, at first sight, are largely

https://insight.jci.org/posts/83
Survival was projected by stratifying patients according to their p53 mutant-specific residual transcriptional activity scores. RESULTS. Pan-cancer survival analyses revealed a strong association between increased mutant p53 residual activity and improved survival in males with glioma and gastric adenocarcinoma (P = 0.002 and P = 0.02) that

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677253/
Abstract. 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 p53-dependent tumor suppressive functions, but also frequently acquire oncogenic gain

https://www.embopress.org/doi/10.15252/embj.2019102096
The TP53 gene, encoding the tumor‐suppressive transcription factor p53, is mutated in about half of all human cancers. The presence of TP53 mutations correlates in many cancer types with enhanced metastasis and aggressiveness, reduced responses to chemotherapeutic drugs, and, thus, a poor prognosis (Robles et al, 2016; Sabapathy & Lane, 2018).More than 85% of all amino acid positions were

https://www.nature.com/articles/s41419-022-05408-1
Tao Zhang. Molecular Biology Reports (2024) TP53, a crucial tumor suppressor gene, is the most commonly mutated gene in human cancers. Aside from losing its tumor suppressor function, mutant p53

https://www.youtube.com/watch?v=o_S6DgRc3m0
Spontaneous mutations in the gene encoding the tumor suppressor p53 (TP53) are frequently identified in human cancers, and most of these mutations are the re

https://www.nature.com/articles/s41418-023-01253-7
However, GOF mechanisms of mutant p53 action in cancer did not remain undisputed. Two studies, one in human AML cells and one in mouse lymphoma models, emphasized that the primary effect of mutant

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312027/
1.2. Tumor Suppression Role. p53 has a unique and unequivocal tumor suppression role, which has been confirmed by the cancer susceptibility of individuals affected by Li-Fraumeni syndrome, the p53 inactivation in most sporadic human cancers, and the spontaneous tumorigenesis in mice with the p53 gene knocked out [].During tumor development, inherited and/or sporadic TP53 genetic missense

https://www.nature.com/articles/s41388-021-02141-5.pdf
represent tumorigenic p53 mutations that need to be distinguished from other mutations because of their beneficial impact on survival in a therapy context. Oncogene (2022) 41:1011-1023; https

https://pubmed.ncbi.nlm.nih.gov/36400749/
TP53, a crucial tumor suppressor gene, is the most commonly mutated gene in human cancers. Aside from losing its tumor suppressor function, mutant p53 (mutp53) often acquires inherent, novel oncogenic functions, which is termed "gain-of-function". Emerging evidence suggests that mutp53 is highly associated with advanced malignancies and poor

https://www.researchgate.net/publication/326921417_Survival_in_males_with_glioma_and_gastric_adenocarcinoma_correlates_with_mutant_p53_residual_transcriptional_activity
Inversely, p53 mutants with residual activity favor survival in males [100]. The impact of these mutations at the molecular level specifically in GC cells has not been well-characterized, except

https://aacrjournals.org/cancerrescommun/article/1/3/148/665522/Sex-and-Mutation-Specific-p53-Gain-of-Function
In cancer, missense mutations in the DNA-binding domain of TP53 are common. They abrogate canonical p53 activity and frequently confer gain-of-oncogenic function (GOF) through localization of transcriptionally active mutant p53 to noncanonical genes. We found that several recurring p53 mutations exhibit a sex difference in frequency in patients with glioblastoma (GBM). In vitro and in vivo

https://www.sciencedirect.com/science/article/pii/S1549963424000017
Among the tumor suppressor genes, TP53 is the most frequently mutated in human cancers, and most mutations are missense mutations causing production of mutant p53 (mutp53) proteins.TP53 mutations not only results in loss of function (LOH) as a transcription factor and a tumor suppressor, but also gain wild-type p53 (WTp53)-independent oncogenic functions that enhance cancer metastasis and

https://www.cell.com/cancer-cell/fulltext/S1535-6108(14)00037-3
Many different types of cancer show a high incidence of TP53 mutations, leading to the expression of mutant p53 proteins. There is growing evidence that these mutant p53s have both lost wild-type p53 tumor suppressor activity and gained functions that help to contribute to malignant progression. Understanding the functions of mutant p53 will help in the development of new therapeutic

https://www.nature.com/articles/cgt201063
In a knock-in mice harboring the p53 R172H mutant (p53 H), equivalent to the human hot-spot mutant p53 R175H, no p53 accumulation was found in the normal tissues of p53 H/H homozygote mice

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9674619/
Mutp53 types in cancer. TP53 is located on the short arm of human chromosome 17 (17p13.1) and consists of 11 exons, 10 introns and 393 amino acid residues. p53 protein is a transcription factor that is usually divided into three functional domains: the amino-terminal domain, the DNA binding domain and the carboxy-terminal domain [].Wild-type p53 (wtp53) plays pivotal role in many important

https://pubmed.ncbi.nlm.nih.gov/25954247/
Two main mechanisms accounting for mutp53 proto-oncogenic activity are inhibition of the wild-type p53 in a dominant-negative fashion and gain of additional oncogenic activities known as gain-of-function (GOF). Here, we discuss a novel mechanism of mutp53 GOF, which relies on its oncogenic cooperation with the heat shock machinery.

https://pubmed.ncbi.nlm.nih.gov/37877348/
Functional inactivation of wild-type p53 is a major trait of cancerous cells. In many cases, such inactivation occurs by either TP53 gene mutations or due to overexpression of p53 binding partners. This review focuses on an overexpressed p53 binding partner called mortalin, a mitochondrial heat shock protein that sequesters both wild-type and mutant p53 in malignant cells due to changes in

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8709944/
p53 and cancer progression. Mutation in the TP53 gene is detectable in about 50% of human breast, colon, lung, liver, prostate, bladder, and skin cancer. Upon DNA damage, wildtype p53 acts in restraining the process of cell replication until the damage is repaired, thus preventing the propagation of DNA-defective cells and the acquisition of a cancer phenotype (Fig. 1).

https://www.embopress.org/doi/full/10.1038/s44321-024-00077-3
To test the dependency of ATO efficacy on mutant p53 expression in 786-O cells, we knocked down endogenous p53 by shRNA (Fig. EV5H). p53 knockdown induced a slight but significant proliferation defect in 786-O cells (Fig. EV5H), suggesting that at least one of the p53 mutations reported in this cell line acts as a gain-of-function.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8889716/
Here, we report that in p53-deficient leukemia and lymphoma models the effects of E177R expression are entirely opposite: E177R inhibits cell proliferation and viability and induces cancer regression. p53-deficient cancer cells prove to be so addicted to the absence of p53 that the residual activity of E177R is detrimental for cancer growth.