The cyclin-dependent kinase 11^p46 isoform interacts with RanBPM

We identified Ran-binding protein (RanBPM) as an interacting partner of the caspase-processed C-terminal domain of cyclin-dependent kinase 11 (CDK11^p46) by using the yeast two-hybrid system. CDK11 ^p110 protein kinases are members of the cyclin-dependent kinase superfamily. During staurosporine-, Fas-, and tumor necrosis factor α-induced apoptosis caspase-processed activated CDK11^p46 is generated from larger CDK11^p110 isoforms. CDK11^p46 promotes apoptosis when it is ectopically expressed in human cells. However, the mechanism of signal transduction through CDK11^p46 is still unclear. In this study, we demonstrate that CDK11^p46 directly interacts with RanBPM in vitro and in human cells. RanBPM contains a conserved SPRY (repeats in splA and Ryr) domain and is localized both in the nucleus and cytoplasm. The SPRY domain of RanBPM is responsible for the association between CDK11^p46 and RanBPM. Furthermore, we show that CDK11⁴⁶ phosphorylates RanBPM.