Thr-370 Is Responsible for CDK11p58 Autophosphorylation, Dimerization, and Kinase Activity.

CDK11p58, a member of the p34cdc2-related kinase family, is associated with cell cycle progression, tumorigenesis, and proapoptotic signaling. It is also required for the maintenance of chromosome cohesion, the maturation of centrosome, the formation of bipolar spindle, and the completion of mitosis. Here we identified that CDK11p58 interacted with itself to form homodimers in cells, whereas D224N, the kinase-dead mutant, failed to form homodimers. CDK11p58 was autophosphorylated, and the main functions of CDK11p58, such as kinase activity, transactivation of nuclear receptors, and proapoptotic signal transduction, were dependent on its autophosphorylation. Furthermore, the in vitro kinase assay indicated that CDK11p58 was autophosphorylated at Thr-370. By mutagenesis, we created CDK11p58 T370A and CDK11p58 T370D, which mimic the dephosphorylated and phosphorylated forms of CDK11p58, respectively. The T370A mutant could not form dimers and be phosphorylated by the wild type CDK11p58 and finally lost the kinase activity. Further functional research revealed that T370A failed to repress the transactivition of androgen receptor and enhance the cell apoptosis. Overall, our data indicated that Thr-370 is responsible for the autophosphorylation, dimerization, and kinase activity of CDK11p58. Moreover, Thr-370 mutants might affect CDK11p58-mediated signaling pathways. [ABSTRACT FROM AUTHOR]