The p34^cdc2-related cyclin-dependent kinase 11 interacts with the p47 subunit of eukaryotic initiation factor 3 during apoptosis

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 (Ser⁴⁶) 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.