دورية أكاديمية
JNK mediates cell death by promoting the ubiquitination of the apurinic/apyrimidinic endonuclease APE1.
| العنوان: | JNK mediates cell death by promoting the ubiquitination of the apurinic/apyrimidinic endonuclease APE1. |
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| المؤلفون: | Tabanifar B; Divisions of Cellular & Molecular Research, National Cancer Centre Singapore, Singapore 168583, Singapore., Moorthy A; Divisions of Cellular & Molecular Research, National Cancer Centre Singapore, Singapore 168583, Singapore., Tsai HH; Queensland Health Forensic and Scientific Services, Coopers Plains, QLD 4108, Australia., Kannan S; Bioinformatics Institute, ASTAR, Singapore 138671, Singapore., Verma CS; Bioinformatics Institute, ASTAR, Singapore 138671, Singapore; Department of Biological Sciences, National University of Singapore, Singapore 117558, Singapore; School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore., Sabapathy K; Divisions of Cellular & Molecular Research, National Cancer Centre Singapore, Singapore 168583, Singapore; School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore. Electronic address: kanaga.sabapathy@ntu.edu.sg. |
| المصدر: | Cell reports [Cell Rep] 2023 Sep 26; Vol. 42 (9), pp. 113123. Date of Electronic Publication: 2023 Sep 12. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 101573691 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2211-1247 (Electronic) NLM ISO Abbreviation: Cell Rep Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [Cambridge, MA] : Cell Press, c 2012- |
| مواضيع طبية MeSH: | DNA Damage* , Endonucleases* , MAP Kinase Kinase 4*/metabolism, Humans ; Cell Death ; Phosphorylation ; Ubiquitination |
| مستخلص: | The c-Jun-NH2-terminal kinases (JNKs) regulate cell death, generally through the direct phosphorylation of both pro- and anti-apoptotic substrates. In this report, we demonstrate an alternate mechanism of JNK-mediated cell death involving the anti-apoptotic protein human apurinic/apyrimidinic endonuclease 1 (APE1). Treatment of cells with a variety of genotoxic stresses enhanced APE1-JNK (all isoforms of JNK1 or JNK2) interaction, specifically in cells undergoing apoptosis. Steady-state APE1 levels were decreased in these cells, in which APE1 is ubiquitinated and degraded in a JNK-dependent manner. Absence of JNKs reduced APE1 ubiquitination and increased its abundance. Mechanistically, the E3 ligase ITCH associates with both APE1 and JNK and is necessary for JNK-dependent APE1 ubiquitination and degradation. Structural models of the JNK-APE1 interaction support the observation of enhanced association of the complex in the presence of ubiquitin. The data together show a mechanism of JNK-mediated cell death by the degradation of APE1 through ITCH. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: APE1; CP: Molecular biology; ITCH; JNK; apoptosis |
| المشرفين على المادة: | EC 3.1.- (Endonucleases) EC 2.7.12.2 (MAP Kinase Kinase 4) EC 4.2.99.18 (APEX1 protein, human) |
| تواريخ الأحداث: | Date Created: 20230913 Date Completed: 20231011 Latest Revision: 20231014 |
| رمز التحديث: | 20240829 |
| DOI: | 10.1016/j.celrep.2023.113123 |
| PMID: | 37703179 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2211-1247 |
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| DOI: | 10.1016/j.celrep.2023.113123 |