{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T13:04:42Z","timestamp":1792069482388,"version":"4.4.0"},"reference-count":43,"publisher":"National Academy of Sciences","issue":"21","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2009,5,26]]},"abstract":"<jats:p>\n                    ASC-2, a multifunctional coactivator, forms a steady-state complex, named ASCOM (for\n                    <jats:italic>AS<\/jats:italic>\n                    C-2\n                    <jats:italic>COM<\/jats:italic>\n                    plex), that contains the histone H3-lysine-4 (H3K4)-methyltransferase MLL3 or its paralogue MLL4. Somewhat surprisingly, given prior indications of redundancy between MLL3 and MLL4, targeted inactivation of the MLL3 H3K4-methylation activity in mice is found to result in ureter epithelial tumors. Interestingly, this phenotype is exacerbated in a\n                    <jats:italic>p53<\/jats:italic>\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    background and the tumorigenic cells are heavily immunostained for \u03b3H2AX, indicating a contribution of MLL3 to the DNA damage response pathway through p53. Consistent with the in vivo observations, and the demonstration of a direct interaction between p53 and ASCOM, cell-based assays have revealed that ASCOM, through ASC-2 and MLL3\/4, acts as a p53 coactivator and is required for H3K4-trimethyation and expression of endogenous p53-target genes in response to the DNA damaging agent doxorubicin. In support of redundant functions for MLL3 and MLL4 for some events, siRNA-mediated down-regulation of both MLL3 and MLL4 is required to suppress doxorubicin-inducible expression of several p53-target genes. Importantly, this study identifies a specific H3K4 methytransferase complex, ASCOM, as a physiologically relevant coactivator for p53 and implicates ASCOM in the p53 tumor suppression pathway in vivo.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0902873106","type":"journal-article","created":{"date-parts":[[2009,5,11]],"date-time":"2009-05-11T21:43:15Z","timestamp":1242078195000},"page":"8513-8518","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":194,"title":["A tumor suppressive coactivator complex of p53 containing ASC-2 and histone H3-lysine-4 methyltransferase MLL3 or its paralogue MLL4"],"prefix":"10.1073","volume":"106","author":[{"given":"Jeongkyung","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dae-Hwan","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seunghee","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi-Heng","family":"Yang","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, 1230 York Avenue, New York, NY 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong Kee","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soo-Kyung","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert G.","family":"Roeder","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, 1230 York Avenue, New York, NY 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae W.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2009,5,26]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1210\/er.2004-0012"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00451-07"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.75.103004.142422"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01080"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1076"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2006.12.014"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.23.1.140-149.2003"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0607313103"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M701574200"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01506-06"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature06192"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1149042"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature06145"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0707292104"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.24.11.4994-5004.2004"},{"key":"e_1_3_3_16_2","first-page":"3441","article-title":"Independent amplification and frequent co-amplification of three nonsyntenic regions on the long arm of chromosome 20 in human breast cancer","volume":"56","author":"Tanner MM","year":"1996","unstructured":"MM Tanner, et al., Independent amplification and frequent co-amplification of three nonsyntenic regions on the long arm of chromosome 20 in human breast cancer. 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