Article: article from journal or magazin.
Species selectivity of mixed-lineage leukemia/trithorax and HCF proteolytic maturation pathways.
Molecular and Cellular Biology
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-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.
Amino Acid Sequence, Animals, Chromosomal Proteins, Non-Histone/genetics, Chromosomal Proteins, Non-Histone/metabolism, Drosophila Proteins/genetics, Drosophila Proteins/metabolism, Drosophila melanogaster/genetics, Drosophila melanogaster/metabolism, Endopeptidases/genetics, Endopeptidases/metabolism, Enzyme Stability, Evolution, Molecular, Hela Cells, Humans, Mice, Molecular Sequence Data, Myeloid-Lymphoid Leukemia Protein/genetics, Myeloid-Lymphoid Leukemia Protein/metabolism, Protease Inhibitors/metabolism, Protein Precursors/genetics, Protein Precursors/metabolism, RNA Interference, Sequence Alignment, Substrate Specificity
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