دورية أكاديمية
أعرض في EDS

PARK2 suppresses the proliferation of high-grade serous ovarian carcinoma via inducing the proteasomal degradation of ZNF703.

التفاصيل البيبلوغرافية
العنوان: PARK2 suppresses the proliferation of high-grade serous ovarian carcinoma via inducing the proteasomal degradation of ZNF703.
المؤلفون: Wang F; Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, Heilongjiang, China.; Department of Obstetrics and Gynecology, The Sixth Affiliated Hospital of Harbin Medical University, Harbin, 152000, Heilongjiang, China., Li Y; Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, Heilongjiang, China., Han Y; Department of Obstetrics and Gynecology, The Sixth Affiliated Hospital of Harbin Medical University, Harbin, 152000, Heilongjiang, China., Zhang Y; Department of Obstetrics and Gynecology, The Sixth Affiliated Hospital of Harbin Medical University, Harbin, 152000, Heilongjiang, China., Wang H; Department of Obstetrics and Gynecology, The Sixth Affiliated Hospital of Harbin Medical University, Harbin, 152000, Heilongjiang, China., Wang L; Department of Diagnostic Ultrasound, The Sixth Affiliated Hospital of Harbin Medical University, Harbin, 152000, Heilongjiang, China., Wang C; Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, Heilongjiang, China., Guo M; Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, Heilongjiang, China., Li P; Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, Heilongjiang, China. peiley@hrbmu.edu.cn.
المصدر: Medical oncology (Northwood, London, England) [Med Oncol] 2024 Jul 23; Vol. 41 (8), pp. 207. Date of Electronic Publication: 2024 Jul 23.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Springer Country of Publication: United States NLM ID: 9435512 Publication Model: Electronic Cited Medium: Internet ISSN: 1559-131X (Electronic) Linking ISSN: 13570560 NLM ISO Abbreviation: Med Oncol Subsets: MEDLINE
أسماء مطبوعة: Publication: 2011- : New York : Springer
Original Publication: Northwood, Middlesex, England : Science and Technology Letters, c1994-
مواضيع طبية MeSH: Ovarian Neoplasms*/pathology , Ovarian Neoplasms*/metabolism , Ovarian Neoplasms*/genetics , Ubiquitin-Protein Ligases*/metabolism , Ubiquitin-Protein Ligases*/genetics , Cell Proliferation* , Proteasome Endopeptidase Complex*/metabolism , Cystadenocarcinoma, Serous*/pathology , Cystadenocarcinoma, Serous*/metabolism , Cystadenocarcinoma, Serous*/genetics, Humans ; Female ; Cell Line, Tumor ; Animals ; Mice ; Ubiquitination ; Cyclin D1/metabolism ; Cyclin D1/genetics ; Oncogene Proteins/metabolism ; Oncogene Proteins/genetics ; Mice, Nude ; Proteolysis ; Cyclin E/metabolism ; Cyclin E/genetics ; Mice, Inbred BALB C ; Xenograft Model Antitumor Assays ; Gene Expression Regulation, Neoplastic ; Carrier Proteins
مستخلص: High-grade serous ovarian cancer (HGSC) is an aggressive disease with poor prognosis. The oncoprotein ZNF703 is implicated in driving HGSC pathogenesis, but factors regulating its abundance remain unclear. In this study, we aim to investigate the potential connection between ZNF703 dysregulation and ubiquitin-mediated protein degradation in HGSC. Bioinformatics prediction was performed using BioGRID database. HGSC representative cell lines were utilized for in vitro and in vivo studies. Results showed that ZNF703 protein was stabilized upon proteasome inhibition, suggesting a regulation via ubiquitination. The ubiquitin E3 ligase PARK2 was found to interact with ZNF703 in a dose-dependent manner, promoting its polyubiquitination and subsequent proteasomal degradation. Re-expression of PARK2 in HGSC cells led to reduced ZNF703 levels together with decreased Cyclin D1/E1 abundance and G1 cell cycle arrest. ZNF703 overexpression alone increased S phase cells, Cyclin D1/E1 levels, and xenograft tumor growth, while co-expression with PARK2 mitigated these oncogenic effects. Collectively, our findings identify ZNF703 as a bona fide substrate of PARK2, reveal a tumor suppressive function for PARK2 in attenuating ZNF703-mediated G1/S transition and HGSC growth through instigating its degradation. This study elucidates a pivotal PARK2-ZNF703 axis with therapeutic implications for targeted intervention in HGSC.
(© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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معلومات مُعتمدة: 82072864 National Natural Science Foundation of China
فهرسة مساهمة: Keywords: High-grade serous ovarian cancer; PARK2; Tumor growth; Ubiquitination; ZNF703
المشرفين على المادة: EC 2.3.2.27 (Ubiquitin-Protein Ligases)
EC 3.4.25.1 (Proteasome Endopeptidase Complex)
EC 2.3.2.27 (parkin protein)
0 (ZNF703 protein, human)
136601-57-5 (Cyclin D1)
0 (Oncogene Proteins)
0 (CCND1 protein, human)
0 (CCNE1 protein, human)
0 (Cyclin E)
0 (Carrier Proteins)
تواريخ الأحداث: Date Created: 20240723 Date Completed: 20240723 Latest Revision: 20240823
رمز التحديث: 20240823
DOI: 10.1007/s12032-024-02395-5
PMID: 39043895
قاعدة البيانات: MEDLINE
الوصف
تدمد:1559-131X
DOI:10.1007/s12032-024-02395-5