Abstract : Mammalian DNA ligase I has been shown to be a phosphoprotein. Dephosphorylation of purified DNA ligase I causes inactivation, an effect dependent on the presence of the N-terminal region of the protein. Expression of full-length human DNA ligase I in Escherichia coli yielded soluble but catalytically inactive enzyme whereas an N-terminally truncated form expressed activity. Incubation of the full-length preparation from E. coli with purified casein kinase II (CKII) resulted in phosphorylation of the N-terminal region and was accompanied by activation of the DNA ligase. Of a variety of purified protein kinases tested, only CKII stimulated the activity of calf thymus DNA ligase I. Tryptic phosphopeptide analysis of DNA ligase I revealed that CKII specifically phosphorylated a major peptide also apparently phosphorylated in cells, implying that CKII is a protein kinase acting on DNA ligase I in the cell nucleus. These data suggest that DNA ligase I is negatively regulated by its N-terminal region and that this inhibition can be relieved by post-translational modification.
http://www.hal.inserm.fr/inserm-00966023
Contributeur : Claude Prigent
<>
Soumis le : mercredi 26 mars 2014 - 08:23:22
Dernière modification le : jeudi 13 septembre 2018 - 16:32:11
Claude Prigent, Dana Lasko, Ken-Ichi Kodama, James Woodgett, Tomas Lindahl. Activation of mammalian DNA ligase I through phosphorylation by casein kinase II.. EMBO Journal, EMBO Press, 1992, 11 (8), pp.2925-33. 〈inserm-00966023〉
