{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T20:00:49Z","timestamp":1787601649162,"version":"build-2736575974"},"reference-count":51,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T00:00:00Z","timestamp":1758758400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Cellular responses after oxidative stress\u2010induced deoxyribonucleic acid (DNA) damage (e.g., DNA double\u2010strand break) control tumor cell proliferation, senescence, and apoptosis. The nuclear ubiquitous casein kinase and cyclin\u2010dependent kinase substrate 1 (NUCKS1) ensures replication feasibility by modulating double\u2010strand break repair necessary to regulate tumor cell proliferation. However, the regulatory mechanism of NUCKS1 in oxidative stress\u2010induced melanoma cell apoptosis is not well characterized. In this study, we reported reduced phosphorylation of NUCKS1 during oxidative stress\u2010mediated melanoma A375 and A875 cell apoptosis, and silencing of NUCKS1 obviously promoted A375 and A875 cell apoptosis. Mechanistically, cyclin\u2010dependent kinase 13 (CDK13) was identified as a major upstream kinase to phosphorylate NUCKS1 and downregulated via ataxia telangiectasia mutated (ATM)\/checkpoint kinase 2 (Chk2)\/cell division cycle 25C (Cdc25C) axis during the process of oxidative stress\u2010induced apoptosis. Moreover, we found that p\u2010NUCKS1 could bind to tyrosine 3\u2010monooxygenase\/tryptophan 5\u2010monooxygenase activation protein Zeta (YWHAZ) and subsequently regulate the level of BCL2\u2010associated X (Bax), thereby leading to melanoma A375 and A875 cell apoptosis. Furthermore, we found that p\u2010NUCKS1 was highly expressed in tumor specimens from melanoma patients, and silencing of NUCKS1 inhibited tumor growth in melanoma A375 and A875\u2010bearing mouse models. Therefore, p\u2010NUCKS1 could act as a potential target for melanoma treatment by mediating oxidative stress\u2010induced apoptosis.<\/jats:p>","DOI":"10.1002\/mc.70040","type":"journal-article","created":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T07:06:47Z","timestamp":1758784007000},"page":"2000-2016","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Inhibiting\n                    <b>Cyclin\u2010Dependent Kinase 13<\/b>\n                    \u2010Mediated Nuclear Ubiquitous Casein Kinase and Cyclin\u2010Dependent Kinase Substrate 1 Phosphorylation Facilitates Oxidative Stress\u2010Induced Apoptosis in Melanoma"],"prefix":"10.1002","volume":"64","author":[{"given":"Zhaohai","family":"Pan","sequence":"first","affiliation":[{"name":"Featured Laboratory for Biosynthesis and Target Discovery of Active Components of Traditional Chinese Medicine, School of Traditional Chinese Medicine Binzhou Medical University 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