title: Inhibition of CDK1 activity by sumoylation.
abstract: Sumoylation (a covalent modification by Small Ubiquitin-like Modifiers or SUMO proteins) has been implicated in the regulation of various cellular events including cell cycle progression. We have recently identified CDK1, a master regulator of mitosis and meiosis, as a SUMO target both in vivo and in vitro, supporting growing evidence concerning a close cross talk between sumoylation and phosphorylation during cell cycle progression. However, any data regarding the effect of sumoylation upon CDK1 activity have been missing. In this study, we performed a series of in vitro experiments to inhibit sumoylation by three different means (ginkgolic acid, physiological levels of oxidative stress, and using an siRNA approach) and assessed the changes in CDK1 activity using specific antibodies and a kinase assay. We have also tested for an interaction between SUMO and active and/or inactive CDK1 isoforms in addition to having assessed the status of CDK1-interacting sumoylated proteins upon inhibition of sumoylation. Our data suggest that inhibition of sumoylation increases the activity of CDK1 probably through changes in sumoylated status and/or the ability of specific proteins to bind CDK1 and inhibit its activity.
authors: Department of Biology, Stern College, Yeshiva University, New York, NY, USA.
authors: Yuxuan
authors: Y
authors: Xiao
authors: Department of Biology, Stern College, Yeshiva University, New York, NY, USA.
authors: Benjamin
authors: B
authors: Lucas
authors: Department of Biology, Stern College, Yeshiva University, New York, NY, USA.
authors: Elana
authors: E
authors: Molcho
authors: Department of Biology, Stern College, Yeshiva University, New York, NY, USA.
authors: Tania
authors: T
authors: Schiff
authors: Department of Biology, Stern College, Yeshiva University, New York, NY, USA; Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY, USA. Electronic address: vigodner@yu.edu.
authors: Margarita
authors: M
authors: Vigodner
mesh_terms: D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D047468:Immunoprecipitation; D007527:Isoenzymes / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D058207:Sumoylation
chemical_list: D007527:Isoenzymes; D047428:Protein Kinase Inhibitors; D016203:CDC2 Protein Kinase
keywords: CDK1; Ginkgolic acid; H(2)O(2); Phosphorylation; Sumoylation; siRNA