calpain-catalyzed proteolysis of human dutpase specifically removes the nuclear localization signal peptidecalpain-catalyzed蛋白质水解的人类dutpase专门去除核本地化信号肽.pdfVIP

Calpain-Catalyzed Proteolysis of Human dUTPase Specifically Removes the Nuclear Localization Signal Peptide ´ ´ 1. ´ 1. ´ 2 2,3 ´ ´ 1 ´ Zoltan Bozoky , Gergely Rona , Eva Klement , Katalin F. Medzihradszky , Gabor Merenyi , Beata G. ´ 1,4 1 Vertessy *, Peter Friedrich * 1 Institute of Enzymology, Hungarian Academy of Sciences, Budapest, Hungary, 2 Proteomics Research Group, Biological Research Centre (BRC), Hungarian Academy of Sciences, Szeged, Hungary, 3 Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California, United States of America, 4 Department of Applied Biotechnology, Budapest University of Technology and Economics, Budapest, Hungary Abstract Background: Calpain proteases drive intracellular signal transduction via specific proteolysis of multiple substrates upon Ca2+-induced activation. Recently, dUTPase, an enzyme essential to maintain genomic integrity, was identified as a physiological calpain substrate in Drosophila cells. Here we investigate the potential structural/functional significance of calpain-activated proteolysis of human dUTPase. Methodology/Principal Findings: Limited proteolysis of human dUTPase by mammalian m-calpain was investigated in the presence and absence of cognate ligands of either calpain or dUTPase. Significant proteolysis was observed only in the presence of Ca(II) ions, inducing calpain action. The presence or absence of the dUTP-analogue a,b-imido-dUTP did not show any effect on Ca2+-calpain-induced cleavage of human dUTPase. The catalytic