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The clinical importance of assessing and combining data on TP53 mutations and isoforms is discussed in this article. It gives a succinct overview of the structural makeup and key biological roles of the isoforms. It then provides a comprehensive summary of the roles that p53 isoforms play in cancer development, therapy response and resistance. The review provides a summary of studies demonstrating the role of p53 isoforms as potential prognostic indicators. It further provides evidence on how the presence of TP53 mutations may affect one or more of these activities and the association of p53 isoforms with clinicopathological data in various tumour types. The review gives insight into the present diagnostic hurdles for identifying TP53 isoforms and makes recommendations to improve their evaluation. In conclusion, this review offers suggestions for enhancing the identification and integration of TP53 isoforms in conjunction with mutation data within the clinical context.
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http://dx.doi.org/10.1016/j.pathol.2024.02.003 | DOI Listing |
Elife
September 2025
Institute of Biophysical Chemistry and Center for Biomolecular Magnetic Resonance, Goethe University, Frankfurt am Main, Germany.
The p53 transcription factor family consists of the three members p53, p63, and p73. Both p63 and p73 exist in different isoforms that are well characterized. Isoforms have also been identified for p53 and it has been proposed that they are responsible for increased cancer metastasis.
View Article and Find Full Text PDFCell Signal
September 2025
Departments of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN 38163, USA. Electronic address:
Mature mRNAs are generated by spliceosomes that recruit factors to aid RNA splicing in which introns are removed and exons joined. Among the splicing factors, a family of proteins contain a homologous U2 Auxiliary Factor (U2AF) Homology Motif (UHM) to bind with factors containing U2AF ligand motifs (ULM) and recruit them to regulate 3' splice site selection. Mutations and overexpression of UHM splicing factors are frequently found in cancers.
View Article and Find Full Text PDFFront Oncol
August 2025
Department of Pathology, West China Hospital, Sichuan University, Chengdu, China.
In this study, we retrospectively analyzed the clinicopathological features of a case of hepatic infantile hemangioma (HIH) that malignantly transformed into hemangiosarcoma. HIH, a congenital disease, is the most common benign tumor of the liver in children, and its malignant transformation into hepatic angiosarcoma (HAS) is rare. HIH expresses markers of vascular origin and specifically expresses glucose transporter protein isoform 1.
View Article and Find Full Text PDFp53 isoforms remain poorly characterized despite recent evidence that they possess distinct functions in response to different cellular stresses. In , four p53 isoforms are expressed from a single locus, but their individual roles under different stress conditions are not yet fully understood, partly due to limited tools for isoform-specific analysis. To address this gap, we developed and validated a set of isoform-specific qPCR primers that accurately distinguish all endogenous p53 transcripts.
View Article and Find Full Text PDFFEBS J
August 2025
Department of Neurosciences, Biomedicine and Movement Sciences, Section of Biochemistry, University of Verona, Italy.
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer marked by poor prognosis and frequent gain-of-function mutations in the TP53 tumor suppressor gene. Given the crucial role of mutant p53 in the context of metabolic reprogramming and aggressive tumor behavior, we explored its role on mitochondria, which may present a valuable therapeutic target. In this study, we characterized the unique mitochondrial proteome observed in PDAC cells harboring the gain-of-function TP53 mutation and discovered a strong mutant p53-dependent upregulation of myosin heavy chain 14 (MYH14), a nonmuscle myosin, implicated in mitochondrial dynamics.
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