title: The p34cdc2-related cyclin-dependent kinase 11 interacts with the p47 subunit of eukaryotic initiation factor 3 during apoptosis.
abstract: Cyclin-dependent kinase 11 (CDK11; also named PITSLRE) is part of the large family of p34(cdc2)-related kinases whose functions appear to be linked with cell cycle progression, tumorigenesis, and apoptotic signaling. However, substrates of CDK11 during apoptosis have not been identified. We used a yeast two-hybrid screening strategy and identified eukaryotic initiation factor 3 p47 protein (eIF3 p47) as an interacting partner of caspase-processed C-terminal kinase domain of CDK11 (CDK11(p46)). We demonstrate that the eIF3 p47 can interact with CDK11 in vitro and in vivo, and the interaction can be strengthened by stimulation of apoptosis. EIF3 p47 contains a Mov34/JAB domain and appears to interact with CDK11(p46) through this motif. We show in vitro that the caspase-processed CDK11(p46) can phosphorylate eIF3 p47 at a specific serine residue (Ser(46)) and that eIF3 p47 is phosphorylated in vivo during apoptosis. Purified recombinant CDK11(p46) inhibited translation of a reporter gene in vitro in a dose-dependent manner. In contrast, a kinase-defective mutant CDK11(p46M) did not inhibit translation of the reporter gene. Stable expression of CDK11(p46) in vivo inhibited the synthesis of a transfected luciferase reporter protein and overall cellular protein synthesis. These data provide insight into the cellular function of CDK11 during apoptosis.
authors.affiliation: Department of Pathology, Arizona Cancer Center, University of Arizona, Tucson, Arizona 85724, USA.
authors.forename: Jiaqi
authors.initials: J
authors.lastname: Shi
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Feng
authors.forename: Anne-Christine
authors.initials: AC
authors.lastname: Goulet
authors.forename: Richard R
authors.initials: RR
authors.lastname: Vaillancourt
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Sachs
authors.forename: John W
authors.initials: JW
authors.lastname: Hershey
authors.forename: Mark A
authors.initials: MA
authors.lastname: Nelson
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D018844:Cyclin-Dependent Kinases / Q000502:physiology*; D039621:Eukaryotic Initiation Factor-3 / Q000502:physiology*; D006801:Humans; D009154:Mutation; D010766:Phosphorylation; D011485:Protein Binding; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
chemical_list: D039621:Eukaryotic Initiation Factor-3; D011994:Recombinant Proteins; C447612:CDK11a protein, human; D018844:Cyclin-Dependent Kinases