{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T14:29:17Z","timestamp":1787149757316,"version":"build-2736575974"},"reference-count":22,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T00:00:00Z","timestamp":1748995200000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Biochemistry &amp;amp; Function"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Tumor suppressor RB is a central regulator of cell cycle progression. By binding to E2F transcription factors, RB can inhibit transcription of E2F target genes to cause cell cycle arrest. Cyclin dependent kinases (CDK) regulate the interaction of RB\/E2F by phosphorylating RB at multiple sites. Previously, we observed that CDK2, RB and E2F inhibit ferroptosis. Ferroptosis is a non\u2010apoptotic, iron\u2010dependent form of cell death characterized by toxic lipid peroxidation. Here, we investigate whether RB is a downstream target of CDK activity in the regulation of ferroptosis. We approach this question by overexpressing wild\u2010type (WT) RB or a mutant RB that cannot be phosphorylated by CDKs (RB\u0394CDK) followed by analysis of ferroptosis. Overexpressing WT\u2010RB reduced sensitivity to ferroptosis while the RB\u0394CDK mutant increased sensitivity. As we previously found, increasing CDK2 expression reduced ferroptotic sensitivity. This reduction persisted in cells expressing RB\u0394CDK. However, WT\u2010RB blocked the ability of CDK2 to inhibit ferroptosis. These observations suggest that at least part of the mechanism by which CDK2 inhibits ferroptosis is by phosphorylating RB.<\/jats:p>","DOI":"10.1002\/cbf.70085","type":"journal-article","created":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T01:09:01Z","timestamp":1749085741000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Phosphorylation State of RB Modulates Ferroptotic Sensitivity"],"prefix":"10.1002","volume":"43","author":[{"given":"Nishanth","family":"Kuganesan","sequence":"first","affiliation":[{"name":"Department of Biological Sciences University of Toledo Toledo Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samkeliso","family":"Dlamini","sequence":"additional","affiliation":[{"name":"Department of Medicinal and Biological Chemistry University of Toledo Toledo Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. M. Viranga","family":"Tillekeratne","sequence":"additional","affiliation":[{"name":"Department of Medicinal and Biological Chemistry University of Toledo Toledo Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2798-9600","authenticated-orcid":false,"given":"William R.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences University of Toledo Toledo Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,4]]},"reference":[{"issue":"5","key":"e_1_2_8_2_1","first-page":"897","article-title":"The RB Family of Cell Cycle Regulatory Factors: Clinical Implications","volume":"17","author":"Masciullo V.","year":"2000","journal-title":"International Journal of Oncology"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2504"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2021.101365"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.03.042"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI166647"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2014.11.014"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1039\/C7OB03086J"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-42251-5"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.2c00909"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.201800311"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.02872"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2019.01.004"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.5.2509"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1177\/12.6.451"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.29870"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.091744"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2007.135"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.02307"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.212519499"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1021\/acscentsci.7b00028"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21841-w"},{"key":"e_1_2_8_23_1","first-page":"1","article-title":"Regulation of Ferroptosis by Transcription Factor E2F1 and RB","author":"Kuganesan N.","year":"2023","journal-title":"Research Square"}],"container-title":["Cell Biochemistry and Function"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbf.70085","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T21:30:37Z","timestamp":1760304637000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/cbf.70085"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6]]},"references-count":22,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,6]]}},"alternative-id":["10.1002\/cbf.70085"],"URL":"https:\/\/doi.org\/10.1002\/cbf.70085","archive":["Portico"],"relation":{},"ISSN":["0263-6484","1099-0844"],"issn-type":[{"value":"0263-6484","type":"print"},{"value":"1099-0844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6]]},"assertion":[{"value":"2024-11-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70085"}}