MLL fusion partners AF4 and AF9 interact at subnuclear foci

MLL fusion partners AF4 and AF9 interact at subnuclear foci
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DOI:
10.1038/sj.leu.2403200
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发表时间:
2004-01-01
期刊:
影响因子:
11.4
通讯作者:
Domer, PH
Domer, PH
中科院分区:
医学1区
文献类型:
--
作者:
Erfurth, F;Hemenway, CS;Domer, PH

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MLL基因参与与急性淋巴细胞性白血病和急性髓细胞性白血病相关的易位。这些易位融合MLL与超过30个伴侣基因之一。总的来说,MLL伴侣基因不共享共同的结构基序或生化功能。我们已经鉴定了两种最常见的MLL融合伴侣AF 4和AF 9之间的蛋白质相互作用。这种相互作用仅限于我们命名为“AF 4体”的离散核灶。AF 4体是非核仁的,与我们所研究的任何已知的核结构都不一致。AF 4-AF 9相互作用由MLL-AF 4融合蛋白维持,并且MLL-AF 4融合蛋白的表达可以改变AF 9的亚核定位。鉴于其他研究表明,其他MLL融合伴侣也相互作用,这些结果表明,MLL融合伴侣可能参与蛋白质相互作用的网络具有共同的功能目标。通过与MLL融合破坏这种相互作用网络可能对白血病发生很重要。
The MLL gene is involved in translocations associated with both acute lymphoblastic and acute myelogenous leukemia. These translocations fuse MLL with one of over 30 partner genes. Collectively, the MLL partner genes do not share a common structural motif or biochemical function. We have identified a protein interaction between the two most common MLL fusion partners AF4 and AF9. This interaction is restricted to discrete nuclear foci we have named 'AF4 bodies'. The AF4 body is non-nucleolar and is not coincident with any known nuclear structures we have examined. The AF4-AF9 interaction is maintained by the MLL-AF4 fusion protein, and expression of the MLL-AF4 fusion can alter the subnuclear localization of AF9. In view of other research indicating that other MLL fusion partners also interact with one another, these results suggest that MLL fusion partners may participate in a web of protein interactions with a common functional goal. The disruption of this web of interactions by fusion with MLL may be important to leukemogenesis.