{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T20:01:46Z","timestamp":1791576106574,"version":"4.3.4"},"reference-count":37,"publisher":"National Academy of Sciences","issue":"18","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2012,5]]},"abstract":"<jats:p>The bromodomain protein, BRD4, has been identified recently as a therapeutic target in acute myeloid leukemia, multiple myeloma, Burkitt\u2019s lymphoma, NUT midline carcinoma, colon cancer, and inflammatory disease; its loss is a prognostic signature for metastatic breast cancer. BRD4 also contributes to regulation of both cell cycle and transcription of oncogenes, HIV, and human papilloma virus (HPV). Despite its role in a broad range of biological processes, the precise molecular mechanism of BRD4 function remains unknown. We report that BRD4 is an atypical kinase that binds to the carboxyl-terminal domain (CTD) of RNA polymerase II and directly phosphorylates its serine 2 (Ser2) sites both in vitro and in vivo under conditions where other CTD kinases are inactive. Phosphorylation of the CTD Ser2 is inhibited in vivo by a BRD4 inhibitor that blocks its binding to chromatin. Our finding that BRD4 is an RNA polymerase II CTD Ser2 kinase implicates it as a regulator of eukaryotic transcription.<\/jats:p>","DOI":"10.1073\/pnas.1120422109","type":"journal-article","created":{"date-parts":[[2012,4,17]],"date-time":"2012-04-17T01:45:25Z","timestamp":1334627125000},"page":"6927-6932","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":356,"title":["BRD4 is an atypical kinase that phosphorylates Serine2 of the RNA Polymerase II carboxy-terminal domain"],"prefix":"10.1073","volume":"109","author":[{"given":"Ballachanda N.","family":"Devaiah","sequence":"first","affiliation":[{"name":"Experimental Immunology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian A.","family":"Lewis","sequence":"additional","affiliation":[{"name":"Metabolism Branches, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasha","family":"Cherman","sequence":"additional","affiliation":[{"name":"Craniofacial and Skeletal Diseases Branch and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael C.","family":"Hewitt","sequence":"additional","affiliation":[{"name":"Constellation Pharmaceuticals, Inc., Cambridge, MA 02142"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian K.","family":"Albrecht","sequence":"additional","affiliation":[{"name":"Constellation Pharmaceuticals, Inc., Cambridge, MA 02142"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela G.","family":"Robey","sequence":"additional","affiliation":[{"name":"Craniofacial and Skeletal Diseases Branch and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiko","family":"Ozato","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Growth Regulation, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"Robert J.","family":"Sims","sequence":"additional","affiliation":[{"name":"Constellation Pharmaceuticals, Inc., Cambridge, MA 02142"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dinah S.","family":"Singer","sequence":"additional","affiliation":[{"name":"Experimental Immunology and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2012,4,16]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.20.17.6537-6549.2000"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10334"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.08.017"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1108190108"},{"key":"e_1_3_3_5_2","first-page":"304","article-title":"BRD4-NUT fusion oncogene: A novel mechanism in aggressive carcinoma","volume":"63","author":"French CA","year":"2003","unstructured":"CA French, et al., BRD4-NUT fusion oncogene: A novel mechanism in aggressive carcinoma. 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