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首页> 外文期刊>Molecular and Cellular Biology >Species Selectivity of Mixed-Lineage Leukemia/Trithorax and HCF Proteolytic Maturation Pathways
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Species Selectivity of Mixed-Lineage Leukemia/Trithorax and HCF Proteolytic Maturation Pathways

机译：混合谱系白血病/胸廓和HCF蛋白水解成熟途径的物种选择性

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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-1PRO 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-1PRO 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.
机译：特定位置的蛋白水解过程在细胞活动的调节中起重要作用。通过裂解产生稳定的异源二聚体的前体刺激了人三胸类混合谱系白血病（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）的细胞周期调控活性。复合体。 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MLL和HCF-1的果蝇同源物，即Trithorax和dHCF，都被 Drosophila taspase 1裂解。尽管它们与人类和高度相关>果蝇 taspase 1蛋白具有同源物种特异性。因此，与taspase 1和MLL / Trithorax蛋白的共同进化相一致，人类taspase 1优先切割MLL，而果蝇 taspase 1优先切割Trithorax。 HCF蛋白在加工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成熟与taspase 1无关。取而代之的是，人类和<非洲>非洲爪蟾 HCF-1 PRO 重复序列在体外被具有新特性的人类蛋白水解活性所裂解。因此，从昆虫到人类，HCF蛋白都可以保持蛋白水解成熟，但是进化出不同的机制。

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