Biochemical analyses of the AF10 protein: The extended LAP/PHD-finger mediates oligomerisation
Biochemical analyses of the AF10 protein: The extended LAP/PHD-finger mediates oligomerisation
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DOI：
10.1006/jmbi.2000.3766
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发表时间：
2000-06-02
影响因子：
5.6
通讯作者：
Saha, V
中科院分区：
文献类型：
--
作者：
Linder, B;Newman, R;Saha, V
白血病的发生与染色质结构的改变有关，染色质结构的改变是由染色体易位破坏的调节因子的相互作用结构域的获得或失去引起的。基因MLL，这种易位事件的目标，形成嵌合融合产物与各种伙伴基因。虽然MLL似乎参与染色质介导的基因调控，但其伴侣基因的功能在很大程度上是推测性的。我们报道了MLL伴侣基因AF10的生化分析及其在白血病发生中的可能作用。据报道，AF10与MLL以外的基因重新排列，导致相同的表型，即髓性白血病。我们在AF10蛋白中发现了一个新的蛋白质-蛋白质相互作用基序，包括延伸的LAP/PHD-finger。该结构域介导重组AF10的同质寡聚化，并在几种蛋白质中保守，包括MLL本身。AF10通过与AT-hook基序的特异性相互作用结合十字形DNA，并通过n端区域定义的二部核定位信号定位到细胞核中。(C) 2000学术出版社…
Leukaemogenesis correlates with alterations in chromatin structure brought about by the gain or loss of interactive domains from regulatory factors that are disrupted by chromosomal translocations. The gene MLL, a target of such translocation events, forms chimaeric fusion products with a variety of partner genes. While MLL appears to be Involved in chromatin-mediated gene regulation, the functions of its partner genes are largely speculative. We report the biochemical analysis of the MLL partner gene AF10 and its possible role in leukaemogenesis. AF10 has been reported to be re-arranged with genes other than MLL leading to the same phenotype, a myeloid leukaemia. We have identified a novel protein-protein interaction motif in the AF10 protein comprising the extended LAP/PHD-finger. This domain mediates homo-oligomerisation of recombinant AF10 and is conserved in several proteins, including MLL itself. AF10 binds cruciform DNA via a specific interaction with an AT-hook motif and is localised to the nucleus by a defined bipartite nuclear localisation signal in the N-terminal region.(C) 2000 Academic Press..