title: Species selectivity of mixed-lineage leukemia/trithorax and HCF proteolytic maturation pathways.
abstract: 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.
authors: Center for Integrative Genomics, University of Lausanne, Génopode Building, 1015 Lausanne, Switzerland.
authors: Francesca
authors: F
authors: Capotosti
authors: James J-D
authors: JJ
authors: Hsieh
authors: Winship
authors: W
authors: Herr
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism*; D004795:Enzyme Stability; D019143:Evolution, Molecular; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics / Q000378:metabolism*; D011480:Protease Inhibitors / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D016415:Sequence Alignment; D013379:Substrate Specificity
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D029721:Drosophila Proteins; D011480:Protease Inhibitors; D011498:Protein Precursors; C473147:host cell factor, Drosophila; C512571:trx protein, Drosophila; D051788:Myeloid-Lymphoid Leukemia Protein; D010450:Endopeptidases; C526349:taspase1, Drosophila; C480823:taspase1, human
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