Species selectivity of mixed-lineage leukemia/trithorax and HCF proteolytic maturation pathways
Species selectivity of mixed-lineage leukemia/trithorax and HCF proteolytic maturation pathways
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DOI：
10.1128/mcb.00769-07
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发表时间：
2007-10-01
影响因子：
5.3
通讯作者：
Herr, Winship
中科院分区：
文献类型：
--
作者：
Capotosti, Francesca;Hsieh, James J. -D.;Herr, Winship
位点特异性蛋白水解加工在细胞活动的调节中起着重要作用。人三胸组混合谱系白血病（MLL）蛋白的组蛋白修饰活性和细胞增殖因子单纯疱疹病毒宿主细胞因子1（HCF-1）的细胞周期调节活性通过产生稳定的异二聚体复合物的前体的切割来刺激。MLL由一种称为taspase 1的蛋白酶加工，而HCF-1成熟的确切机制尚不清楚，尽管已知它们依赖于一系列称为HCF-1（PRO）重复的序列重复。我们在这里证明，果蝇同源MLL和HCF-1，称为Trithorax和dHCF，都被果蝇taspase 1裂解。虽然高度相关，人类和果蝇taspase 1蛋白显示同源物种特异性。因此，人taspase 1优先切割MLL，果蝇taspase 1优先切割Trithorax，这与taspase 1和MLL/Trithorax蛋白的共同进化一致。HCF蛋白在加工过程中表现出更大的物种特异性差异：而dHCF被果蝇taspase 1切割，人类和小鼠HCF-1成熟是taspase 1独立的。相反，人和非洲爪蟾HCF-1（PRO）重复序列在体外被具有新特性的人蛋白水解活性切割。因此，从昆虫到人类，HCF蛋白具有保守的蛋白水解成熟，但进化出不同的机制。
Site-specific proteolytic processing plays important roles in the regulation of cellular activities. The histone modification activity of the human trithorax group mixed-lineage leukemia (MLL) protein and the cell cycle regulatory activity of the cell proliferation factor herpes simplex virus host cell factor 1(HCF-1) are stimulated by cleavage of precursors that generates stable heterodimeric complexes. MLL is processed by a protease called taspase 1, whereas the precise mechanisms of HCF-1 maturation are unclear, although they are known to depend on a series of sequence repeats called HCF-1(PRO) repeats. We demonstrate here that the Drosophila homologs of MLL and HCF-1, called Trithorax and dHCF, are both cleaved by Drosophila taspase 1. Although highly related, the human and Drosophila taspase 1 proteins display cognate species specificity. Thus, human taspase 1 preferentially cleaves MLL and Drosophila taspase 1 preferentially cleaves Trithorax, consistent with coevolution of taspase 1 and MLL/Trithorax proteins. HCF proteins display even greater species-specific divergence in processing: whereas dHCF is cleaved by the Drosophila taspase 1, human and mouse HCF-1 maturation is taspase 1 independent. Instead, human and Xenopus HCF-1(PRO) repeats are cleaved in vitro by a human proteolytic activity with novel properties. Thus, from insects to humans, HCF proteins have conserved proteolytic maturation but evolved different mechanisms.