{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T13:52:21Z","timestamp":1780667541392,"version":"3.54.1"},"reference-count":89,"publisher":"American Society for Clinical Investigation","issue":"10","license":[{"start":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T00:00:00Z","timestamp":1715731200000},"content-version":"vor","delay-in-days":50,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Cancer Institute","award":["P01CA250957"],"award-info":[{"award-number":["P01CA250957"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,5,15]]},"abstract":"<jats:p>\n                    The mammalian SUMO-targeted E3 ubiquitin ligase\n                    <jats:italic>Rnf4<\/jats:italic>\n                    has been reported to act as a regulator of DNA repair, but the importance of RNF4 as a tumor suppressor has not been tested. Using a conditional-knockout mouse model, we deleted\n                    <jats:italic>Rnf4<\/jats:italic>\n                    in the B cell lineage to test the importance of RNF4 for growth of somatic cells. Although\n                    <jats:italic>Rnf4<\/jats:italic>\n                    \u2013conditional-knockout B cells exhibited substantial genomic instability,\n                    <jats:italic>Rnf4<\/jats:italic>\n                    deletion caused no increase in tumor susceptibility. In contrast,\n                    <jats:italic>Rnf4<\/jats:italic>\n                    deletion extended the healthy lifespan of mice expressing an oncogenic c-\n                    <jats:italic>myc<\/jats:italic>\n                    transgene.\n                    <jats:italic>Rnf4<\/jats:italic>\n                    activity is essential for normal DNA replication, and in its absence, there was a failure in ATR-CHK1 signaling of replication stress. Factors that normally mediate replication fork stability, including members of the Fanconi anemia gene family and the helicases PIF1 and RECQL5, showed reduced accumulation at replication forks in the absence of RNF4. RNF4 deficiency also resulted in an accumulation of hyper-SUMOylated proteins in chromatin, including members of the SMC5\/6 complex, which contributes to replication failure by a mechanism dependent on RAD51. These findings indicate that RNF4, which shows increased expression in multiple human tumor types, is a potential target for anticancer therapy, especially in tumors expressing c-\n                    <jats:italic>myc<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1172\/jci167419","type":"journal-article","created":{"date-parts":[[2024,4,11]],"date-time":"2024-04-11T17:20:16Z","timestamp":1712856016000},"source":"Crossref","is-referenced-by-count":14,"title":["RNF4 sustains Myc-driven tumorigenesis by facilitating DNA replication"],"prefix":"10.1172","volume":"134","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8674-2317","authenticated-orcid":true,"given":"Joonyoung","family":"Her","sequence":"first","affiliation":[{"name":"Department of Molecular Biology and Biochemistry and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Zheng","sequence":"additional","affiliation":[{"name":"Biological Mass Spectrometry Facility, 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