دورية أكاديمية
أعرض في EDS

Gain-of-function mutant p53 together with ERG proto-oncogene drive prostate cancer by beta-catenin activation and pyrimidine synthesis.

التفاصيل البيبلوغرافية
العنوان: Gain-of-function mutant p53 together with ERG proto-oncogene drive prostate cancer by beta-catenin activation and pyrimidine synthesis.
المؤلفون: Ding D; Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine and Science, Rochester, MN, 55905, USA., Blee AM; Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine and Science, Rochester, MN, 55905, USA.; Department of Biochemistry, Vanderbilt University, Nashville, TN, 73240, USA., Zhang J; Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine and Science, Rochester, MN, 55905, USA., Pan Y; Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine and Science, Rochester, MN, 55905, USA., Becker NA; Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine and Science, Rochester, MN, 55905, USA., Maher LJ 3rd; Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine and Science, Rochester, MN, 55905, USA., Jimenez R; Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine and Science, Rochester, MN, 55905, USA., Wang L; Division of Biomedical Statistics and Informatics, Mayo Clinic College of Medicine and Science, Rochester, MN, 55905, USA. wang.liguo@mayo.edu., Huang H; Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine and Science, Rochester, MN, 55905, USA. huang.haojie@mayo.edu.; Department of Urology, Mayo Clinic College of Medicine and Science, Rochester, MN, 55905, USA. huang.haojie@mayo.edu.; Mayo Clinic Cancer Center, Mayo Clinic College of Medicine and Science, Rochester, MN, 55905, USA. huang.haojie@mayo.edu.
المصدر: Nature communications [Nat Commun] 2023 Aug 03; Vol. 14 (1), pp. 4671. Date of Electronic Publication: 2023 Aug 03.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : Nature Pub. Group
مواضيع طبية MeSH: Prostatic Neoplasms*/genetics , Prostatic Neoplasms*/metabolism , Transcriptional Regulator ERG*/genetics , Transcriptional Regulator ERG*/metabolism , Tumor Suppressor Protein p53*/genetics , Tumor Suppressor Protein p53*/metabolism, Animals ; Humans ; Male ; Mice ; beta Catenin/genetics ; beta Catenin/metabolism ; Gain of Function Mutation ; Oncogene Proteins, Fusion/genetics ; Proto-Oncogenes ; Pyrimidines/biosynthesis
مستخلص: Whether TMPRSS2-ERG fusion and TP53 gene alteration coordinately promote prostate cancer (PCa) remains unclear. Here we demonstrate that TMPRSS2-ERG fusion and TP53 mutation / deletion co-occur in PCa patient specimens and this co-occurrence accelerates prostatic oncogenesis. p53 gain-of-function (GOF) mutants are now shown to bind to a unique DNA sequence in the CTNNB1 gene promoter and transactivate its expression. ERG and β-Catenin co-occupy sites at pyrimidine synthesis gene (PSG) loci and promote PSG expression, pyrimidine synthesis and PCa growth. β-Catenin inhibition by small molecule inhibitors or oligonucleotide-based PROTAC suppresses TMPRSS2-ERG- and p53 mutant-positive PCa cell growth in vitro and in mice. Our study identifies a gene transactivation function of GOF mutant p53 and reveals β-Catenin as a transcriptional target gene of p53 GOF mutants and a driver and therapeutic target of TMPRSS2-ERG- and p53 GOF mutant-positive PCa.
(© 2023. Springer Nature Limited.)
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معلومات مُعتمدة: R01 CA130908 United States CA NCI NIH HHS; R01 CA134514 United States CA NCI NIH HHS; R01 CA271486 United States CA NCI NIH HHS; R35 GM143949 United States GM NIGMS NIH HHS
المشرفين على المادة: 0 (beta Catenin)
0 (ERG protein, human)
0 (Oncogene Proteins, Fusion)
0 (Pyrimidines)
0 (Transcriptional Regulator ERG)
0 (Tumor Suppressor Protein p53)
0 (TP53 protein, human)
تواريخ الأحداث: Date Created: 20230803 Date Completed: 20230807 Latest Revision: 20240212
رمز التحديث: 20240212
مُعرف محوري في PubMed: PMC10400651
DOI: 10.1038/s41467-023-40352-4
PMID: 37537199
قاعدة البيانات: MEDLINE
الوصف
تدمد:2041-1723
DOI:10.1038/s41467-023-40352-4