{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T16:12:11Z","timestamp":1787587931067,"version":"build-2736575974"},"reference-count":50,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,4,23]],"date-time":"2024-04-23T00:00:00Z","timestamp":1713830400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The St. Louis Men\u2019s Group Against Cancer","award":["#W81XWH-21-1-0203"],"award-info":[{"award-number":["#W81XWH-21-1-0203"]}]},{"name":"The St. Louis Men\u2019s Group Against Cancer","award":["W81XWH-21-1-0202"],"award-info":[{"award-number":["W81XWH-21-1-0202"]}]},{"name":"The St. Louis Men\u2019s Group Against Cancer","award":["1R01CA276502"],"award-info":[{"award-number":["1R01CA276502"]}]},{"name":"The St. Louis Men\u2019s Group Against Cancer","award":["1R01CA273054"],"award-info":[{"award-number":["1R01CA273054"]}]},{"name":"Department of Defense","award":["#W81XWH-21-1-0203"],"award-info":[{"award-number":["#W81XWH-21-1-0203"]}]},{"name":"Department of Defense","award":["W81XWH-21-1-0202"],"award-info":[{"award-number":["W81XWH-21-1-0202"]}]},{"name":"Department of Defense","award":["1R01CA276502"],"award-info":[{"award-number":["1R01CA276502"]}]},{"name":"Department of Defense","award":["1R01CA273054"],"award-info":[{"award-number":["1R01CA273054"]}]},{"name":"NIH\/NCI","award":["#W81XWH-21-1-0203"],"award-info":[{"award-number":["#W81XWH-21-1-0203"]}]},{"name":"NIH\/NCI","award":["W81XWH-21-1-0202"],"award-info":[{"award-number":["W81XWH-21-1-0202"]}]},{"name":"NIH\/NCI","award":["1R01CA276502"],"award-info":[{"award-number":["1R01CA276502"]}]},{"name":"NIH\/NCI","award":["1R01CA273054"],"award-info":[{"award-number":["1R01CA273054"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Advanced localized prostate cancers (PC) recur despite chemotherapy, radiotherapy and\/or androgen deprivation therapy. We recently reported HOXB13 lysine (K)13 acetylation as a gain-of-function modification that regulates interaction with the SWI\/SNF chromatin remodeling complex and is critical for anti-androgen resistance. However, whether acetylated HOXB13 promotes PC cell survival following treatment with genotoxic agents is not known. Herein, we show that K13-acetylated HOXB13 is induced rapidly in PC cells in response to DNA damage induced by irradiation (IR). It colocalizes with the histone variant \u03b3H2AX at sites of double strand breaks (DSBs). Treatment of PCs with the Androgen Receptor (AR) antagonist Enzalutamide (ENZ) did not suppress DNA-damage-induced HOXB13 acetylation. In contrast, HOXB13 depletion or loss of acetylation overcame resistance of PC cells to ENZ and synergized with IR. HOXB13K13A mutants show diminished replication fork progression, impaired G2\/M arrest with significant cell death following DNA damage. Mechanistically, we found that amino terminus regulates HOXB13 nuclear puncta formation that is essential for proper DNA damage response. Therefore, targeting HOXB13 acetylation with CBP\/p300 inhibitors in combination with DNA damaging therapy may be an effective strategy to overcome anti-androgen resistance of PCs.<\/jats:p>","DOI":"10.3390\/cancers16091622","type":"journal-article","created":{"date-parts":[[2024,4,23]],"date-time":"2024-04-23T08:08:27Z","timestamp":1713859707000},"page":"1622","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Amino Terminal Acetylation of HOXB13 Regulates the DNA Damage Response in Prostate Cancer"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0207-2166","authenticated-orcid":false,"given":"Duy T.","family":"Nguyen","sequence":"first","affiliation":[{"name":"Division of Urologic Surgery, Department of Surgery, Washington University in St. Louis, St. Louis, MO 63110, USA"},{"name":"Mayo Clinic Graduate School of Biomedical Sciences, Jacksonville, FL 32224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Urvashi","family":"Mahajan","sequence":"additional","affiliation":[{"name":"Division of Urologic Surgery, Department of Surgery, Washington University in St. Louis, St. Louis, MO 63110, USA"},{"name":"A.T. Still University of Health Sciences, Kirksville, MO 63501, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duminduni Hewa","family":"Angappulige","sequence":"additional","affiliation":[{"name":"Division of Urologic Surgery, Department of Surgery, Washington University in St. Louis, St. Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aashna","family":"Doshi","sequence":"additional","affiliation":[{"name":"Division of Urologic Surgery, Department of Surgery, Washington University in St. Louis, St. Louis, MO 63110, USA"},{"name":"Department of Biochemistry, University of Washington, Seattle, WA 98195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nupam P.","family":"Mahajan","sequence":"additional","affiliation":[{"name":"Division of Urologic Surgery, Department of Surgery, Washington University in St. Louis, St. Louis, MO 63110, USA"},{"name":"Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7192-396X","authenticated-orcid":false,"given":"Kiran","family":"Mahajan","sequence":"additional","affiliation":[{"name":"Division of Urologic Surgery, Department of Surgery, Washington University in St. Louis, St. Louis, MO 63110, USA"},{"name":"Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17","DOI":"10.3322\/caac.21763","article-title":"Cancer statistics, 2023","volume":"73","author":"Siegel","year":"2023","journal-title":"CA Cancer J. 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