We found that a mouse p53 cDNA clone (pP53-5; Jenkins et al, Nature 312: 651-654, 1984), which previously was characterized as encoding mutant p53 protein, in fact represents wild-type mouse p53 cDNA, as we were able to demonstrate that the mutations described represented sequencing artefacts (compressions). Such sequencing artefacts were also observed with a p53 cDNA isolated from mouse T3T3 cells, encoding a mutant p53 with an Arg-Cys exchange at position 270, and could be resolved by sequencing of the opposite DNA strands. As pP53-5 had been successfully used in cellular immortalization and transformation assays (Jenkins et al, Nature 312: 651-654, 1984; Nature 317: 816-818, 1985), our results suggest that wild-type p53 under certain circumstances can induce transformation. This finding is relevant to the recent findings of overexpressed wild-type p53 in human tumors.
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http://dx.doi.org/10.3892/ijo.3.1.23 | DOI Listing |
Curr Oncol
January 2025
Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
The aim of this study was to evaluate associations between TP53 status and outcomes after transarterial embolization (TAE) for the treatment of patients with hepatocellular carcinoma (HCC). This single-institution study included patients from 1/2014 to 6/2022 who underwent TAE of HCC and genomic analysis of tumoral tissue. The primary outcome was overall survival (OS) with relation to TP53 status, and the secondary outcome was the time to progression.
View Article and Find Full Text PDFProteomes
January 2025
Instituto de Matemática e Estatística, Departamento de Ciência da Computação, Universidade de São Paulo, Rua do Matão 1010, São Paulo 05508-090, SP, Brazil.
The tumor suppressor p53, in its wild-type form, plays a central role in cellular homeostasis by regulating senescence, apoptosis, and autophagy within the DNA damage response (DDR). Recent findings suggest that wild-type p53 also governs ferroptosis, an iron-dependent cell death process driven by lipid peroxidation. Post-translational modifications of p53 generate proteoforms that significantly enhance its functional diversity in regulating these mechanisms.
View Article and Find Full Text PDFVirchows Arch
January 2025
Department of Pathology and Molecular Medicine, Thomayer University Hospital, Third Faculty of Medicine, Charles University, Prague, Czech Republic.
Extrapulmonary small cell neuroendocrine carcinoma (EP-SCNC) is a rare malignancy with a poor prognosis. Despite its morphological similarity to lung small cell carcinomas, its oncogenesis remains uncertain. One hundred and seventy-one EP-SCNC were enrolled in a multicenter study, and all tissue samples underwent an immunohistochemical p53 analysis.
View Article and Find Full Text PDFCell Death Dis
January 2025
Department of Clinical and Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan.
The spatial role of M1 and M2 tumor-associated macrophages (M1/M2 TAMs) in precision medicine remains unclear. EGFR and TP53 are among the most frequently mutated genes in lung adenocarcinoma. We characterized the mutation status and density of M1/M2 TAMs within tumor islets and stroma in 117 lung adenocarcinomas using next-generation sequencing and immunohistochemistry, respectively.
View Article and Find Full Text PDFProtein Sci
February 2025
Instituto de Biocomputación y Física de Sistemas Complejos (BIFI), Universidad de Zaragoza, Zaragoza, Spain.
PADI4 is one of the human isoforms of a family of enzymes involved in the conversion of arginine to citrulline. MDM2 is an E3 ubiquitin ligase that is critical for degradation of the tumor suppressor gene p53. We have previously shown that there is an interaction between MDM2 and PADI4 in cellulo, and that such interaction occurs through the N-terminal region of MDM2, N-MDM2, and in particular through residues Thr26, Val28, Phe91, and Lys98.
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