ArticleMolecular cell2017
Mutant p53 Gains Its Function via c-Myc Activation upon CDK4 Phosphorylation at Serine 249 and Consequent PIN1 Binding.
Article in Molecular cell, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 108 citations in OpenAlex.
- A Personalized Therapeutic Approach for Liver Cancers Expressing the African-Centric P47S Variant of TP53.Molecular cancer research : MCR · 2026Article
- Critical Role for Malic Enzymes in MYC-Mediated Cellular Adaptation to Glutamine Depletion.Metabolites · 2026Article
- Cyclic di-GMP suppresses cancer metastasis by targeting proteasome 26S subunit non-ATPase 3 independently of STING.Signal transduction and targeted therapy · 2026Article
- Expression and Clinical Significance of the MRPS5 Gene in Uterine Corpus Endometrial Carcinoma: A Comprehensive Study Based on Public Databases.International journal of women's health · 2026Article
- Deciphering TICRR's oncogenic landscape in pancreatic adenocarcinoma: molecular insights and clinical implications.Discover oncology · 2025Article
- Article
- Cooperation Between Aflatoxin-Induced p53 Aberrations and Hepatitis B Virus in Hepatocellular Carcinoma.Journal of xenobiotics · 2025Review
- Tripartite motif-containing protein 26 promotes colorectal cancer growth by inactivating p53.Cell death and differentiation · 2025Article
- USP33 Regulates DNA Damage Response and Carcinogenesis Through Deubiquitylating and Stabilising p53.Cell proliferation · 2025Article
- PDCD11 Stabilizes C-MYC Oncoprotein by Hindering C-MYC-SKP2 Negative Feedback Loop to Facilitate Progression of p53-Mutant Breast and Colon Malignancies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- CDK4 inactivation inhibits apoptosis via mitochondria-ER contact remodeling in triple-negative breast cancer.Nature communications · 2025Article
- OTUD7B is a new deubiquitinase targeting p53.Theranostics · 2025Article
- p53 enhances elesclomol-Cu-induced cuproptosis in hepatocellular carcinoma via FDXR-mediated FDX1 upregulation.Frontiers in oncology · 2025Article
- CircCFL1 Promotes TNBC Stemness and Immunoescape via Deacetylation-Mediated c-Myc Deubiquitylation to Facilitate Mutant TP53 Transcription.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- A common druggable signature of oncogenic c-Myc, mutant KRAS and mutant p53 reveals functional redundancy and competition among oncogenes in cancer.Cell death & disease · 2024Article
- p53 Genetics and Biology in Lung Carcinomas: Insights, Implications and Clinical Applications.Biomedicines · 2024Review
- SAHA/5-AZA Enhances Acetylation and Degradation of mutp53, Upregulates p21 and Downregulates c-Myc and BRCA-1 in Pancreatic Cancer Cells.International journal of molecular sciences · 2024Article
- Pin1-catalyzed conformational regulation after phosphorylation: A distinct checkpoint in cell signaling and drug discovery.Science signaling · 2024Review
- Construction of a TP53 mutation-associated ceRNA network as prognostic biomarkers in hepatocellular carcinoma.Heliyon · 2024Article
- Tripartite motif-containing protein 26 promotes colorectal cancer growth by inactivating p53.Research square · 2024Article
14 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
TP53 missense mutations significantly influence the development and progression of various human cancers via their gain of new functions (GOF) through different mechanisms. Here we report a unique mechanism underlying the GOF of p53-R249S (p53-RS), a p53 mutant frequently detected in human hepatocellular carcinoma (HCC) that is highly related to hepatitis B infection and aflatoxin B1. A CDK inhibitor blocks p53-RS's nuclear translocation in HCC, whereas CDK4 interacts with p53-RS in the G1/S phase of the cells, phosphorylates it, and enhances its nuclear localization. This is coupled with binding of a peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) to p53-RS, but not the p53 form with mutations of four serines/threonines previously shown to be crucial for PIN1 binding. As a result, p53-RS interacts with c-Myc and enhances c-Myc-dependent rDNA transcription key for ribosomal biogenesis. These results unveil a CDK4-PIN1-p53-RS-c-Myc pathway as a novel mechanism for the GOF of p53-RS in HCC.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.