CDK11p46 and RPS8 associate with each other and suppress translation in a synergistic manner

CDK11p46, a 46 kDa isoform of the PITSLRE kinase family, is a key mediator of cell apoptosis, while the precise mechanism remains to be elucidated. By using His pull-down and mass spectrometry analysis, we identified the ribosomal protein S8 (RPS8), a member of the small subunit ribosome, as an interacting partner of CDK11p46. Further analysis confirmed the association of CDK11p46 and RPS8 in vitro and in vivo, and revealed that RPS8 was not a substrate of CDK11p46. Moreover, RPS8 and CDK11p46 synergize to inhibit the translation process both in cap- and internal ribosomal entry site (IRES)-dependent way, and sensitize cells to Fas ligand-induced apoptosis. Taken together, our results provide evidence for the novel role of CDK11p46 in the regulation of translation and cell apoptosis.

► We identify RPS8 as a novel interacting partner of CDK11p46.
► CDK11p46 and RPS8 synergistically regulate protein synthesis.
► CDK11p46 synergizes with RPS8 to promote celluar apoptosis induced by Fas ligand.