AFF4，ELLE/P-TEFb 延伸复合物的一个组成部分和 MLL 嵌合体的一个共享亚基，可将转录延伸与白血病联系起来。
AFF4, a component of the ELL/P-TEFb elongation complex and a shared subunit of MLL chimeras, can link transcription elongation to leukemia.
机构信息
Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA.
出版信息
Mol Cell. 2010 Feb 12;37(3):429-37. doi: 10.1016/j.molcel.2010.01.026.
Chromosomal translocations involving the MLL gene are associated with infant acute lymphoblastic and mixed lineage leukemia. There are a large number of translocation partners of MLL that share very little sequence or seemingly functional similarities; however, their translocations into MLL result in the pathogenesis of leukemia. To define the molecular reason why these translocations result in the pathogenesis of leukemia, we purified several of the commonly occurring MLL chimeras. We have identified super elongation complex (SEC) associated with all chimeras purified. SEC includes ELL, P-TEFb, AFF4, and several other factors. AFF4 is required for SEC stability and proper transcription by poised RNA polymerase II in metazoans. Knockdown of AFF4 in leukemic cells shows reduction in MLL chimera target gene expression, suggesting that AFF4/SEC could be a key regulator in the pathogenesis of leukemia through many of the MLL partners.
涉及 MLL 基因的染色体易位与婴儿急性淋巴细胞白血病和混合谱系白血病有关。有大量的 MLL 易位伙伴，它们的序列或功能相似性很少；然而，它们易位到 MLL 导致了白血病的发病机制。为了确定这些易位导致白血病发病机制的分子原因，我们纯化了几种常见的 MLL 嵌合体。我们已经鉴定出与所有纯化的嵌合体相关的超延伸复合物（SEC）。SEC 包括 ELL、P-TEFb、AFF4 和其他几个因子。AFF4 在真核生物中稳定 SEC 和处于静止状态的 RNA 聚合酶 II 的正确转录是必需的。在白血病细胞中敲低 AFF4 显示 MLL 嵌合体靶基因表达减少，这表明 AFF4/SEC 可能通过许多 MLL 伙伴成为白血病发病机制中的关键调节剂。
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