PAF 复合物与 HOX 基因座上的 MLL 融合蛋白协同作用，促进白血病发生。
The PAF complex synergizes with MLL fusion proteins at HOX loci to promote leukemogenesis.
机构信息
Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
出版信息
Cancer Cell. 2010 Jun 15;17(6):609-21. doi: 10.1016/j.ccr.2010.04.012.
MLL is involved in chromosomal rearrangements that generate fusion proteins with deregulated transcriptional activity. The mechanisms of MLL fusion protein-mediated transcriptional activation are poorly understood. Here we show MLL interacts directly with the polymerase associated factor complex (PAFc) through sequences flanking the CxxC domain. PAFc interacts with RNA polymerase II and stimulates posttranslational histone modifications. PAFc augments MLL and MLL-AF9 mediated transcriptional activation of Hoxa9. Conversely, knockdown of PAFc disrupts MLL fusion protein-mediated transcriptional activation and MLL recruitment to target loci. PAFc gene expression is downregulated during hematopoiesis and likely serves to regulate MLL function. Deletions of MLL that abolish interactions with PAFc also eliminate MLL-AF9 mediated immortalization indicating an essential function for this interaction in leukemogenesis.
MLL 参与染色体重排，产生转录活性失调的融合蛋白。MLL 融合蛋白介导的转录激活机制尚未完全了解。在这里，我们通过 CxxC 结构域侧翼的序列显示 MLL 与聚合酶相关因子复合物 (PAFc) 直接相互作用。PAFc 与 RNA 聚合酶 II 相互作用并刺激翻译后组蛋白修饰。PAFc 增强了 MLL 和 MLL-AF9 对 Hoxa9 的转录激活。相反，PAFc 的敲低会破坏 MLL 融合蛋白介导的转录激活和 MLL 募集到靶基因座。PAFc 的基因表达在造血过程中下调，可能用于调节 MLL 功能。消除与 PAFc 相互作用的 MLL 缺失也消除了 MLL-AF9 介导的永生化，表明这种相互作用在白血病发生中具有重要功能。
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