Our study reveals that DNAJA1 controls the fate of misfolded mutp53, provides insights into potential strategies to deplete mutp53 through the mevalonate pathway-DNAJA1 axis, and highlights the significance of p53 status in impacting statins' efficacy on cancer therapy.
While mutation of the P53 tumour suppressor gene is a common feature of many types of cancer, mutational inactivation of P53 in melanoma is uncommon; however, its function often appears abnormal.
Both her benign and malignant lesions showed molecularly identical TP53 mutations, indicating that significant genetic alterations can occur in BBD and supporting the clonal evolution from BBD to malignancy.
To estimate the importance of the DNE of TP53 mutations, we analysed the percentage of cancer cases showing a single heterozygous mutation of TP53 and searched for a cell line with a single heterozygous mutation of this gene.
One germline TP53 mutation (c.408A > T/p.Gln136His) and two somatic mutations (c.1022T > G/p.Phe341Cys and c.108-109ins22/p.His37fsX13) are novel to human cancer.
Further, knockdown of <i>CDC7</i> significantly abrogates mutant p53-driven cancer phenotypes <i>in vitro</i> and <i>in vivo</i> Importantly, high <i>CDC7</i> expression significantly correlates with p53 mutational status and predicts poor clinical outcome in lung adenocarcinoma patients.
These drugs reduced the basal levels of p53 protein at nanomolar concentrations in a dose-, time-, and cancer cell line-dependent manner, but independent of p53 status of wild-type or mutant.
The p53 tumor suppressor gene is the most commonly mutated gene in human cancer and is a frequent abnormality in oral squamous cell carcinoma and its precancerous lesions.
Our results indicate that mutational mechanisms, in particular TP53 mutations, are associated with work-related exposure to wood dust in sinonasal cancer.
TP53 is the most frequently mutated tumor suppressor gene in cancers and mutant p53 protein (mutp53) can acquire gain of function (GOF) strongly contributing to malignancy.
Here we hypothesize that targeting Zfp148 would unleash p53 activity and protect against cancer development, and test this idea in the APCMin/+ mouse model of intestinal adenomas.
In this review, we focus on recent research on overexpression of mutant p53 in human cancer, with an emphasis on mutant p53 regulation, gain of function of mutant p53 in transcriptional effects, and the diagnostic, prognostic, and predictive value of p53 overexpression in human cancer.
We introduce the p53 protein as an illustration of the complexity of post-translational modifications that may affect one highly connected protein and discuss the possible impact in AML diagnostics if the p53 profile is reflecting cell stress and status of signal transduction systems of the malignancy.
A strong correlation observed between humoral immune response against p53 protein, missense gene mutations and protein accumulation warrants the application of serological p53-Abs as a non-invasive surrogate marker in screening high-risk populations for early detection of malignancy.
277Y mutations have been described in human tumours, and Ewing tumour cells expressing this mutant from the endogenous p53 locus selectively activate transcription from transfected luciferase reporters regulated by TTT-mutant p53 binding sites. p53 mutants with altered sequence specificity have potential advantages for cancer gene therapy: if used to activate transcription of conditionally toxic genes they would allow tumour-targeting by p53, which acts as a sensor for the malignant state, but place control over cell killing in the hands of the clinician.
Though p53 codon 72 single-nucleotide polymorphism (SNP) did not affect general cancer risk or age of onset, arginine homozygozity, in contrast to proline homozygozity, was found to decrease breast cancer risk in the later onset sporadic cases.