CDC2L5, a Cdk-like kinase with RS domain, interacts with the ASF/SF2-associated protein p32 and affects splicing in vivo

The human CDC2L5 gene encodes a protein of unknown physiological function. This protein is closely related to the cyclin‐dependent kinase (Cdks) family and contains an arginine/serine‐rich (RS) domain. The Cdks were first identified as crucial regulators of cell‐cycle progression, more recently they were found to be involved in transcription and mRNA processing. RS domains are mainly present in proteins regulating pre‐mRNA splicing, suggesting CDC2L5 having a possible role in this process. In this study, we demonstrate that CDC2L5 is located in the nucleoplasm, at a higher concentration in speckles, the storage sites for splicing factors. Furthermore, this localization is dependent on the presence of the N‐terminal sequence including the RS domain. Then, we report that CDC2L5 directly interacts with the ASF/SF2‐associated protein p32, a protein involved in splicing regulation. Overexpression of CDC2L5 constructs disturbs constitutive splicing and switches alternative splice site selection in vivo. These results argue in favor of a functional role of the CDC2L5 kinase in splicing regulation. J. Cell. Biochem. 99: 890–904, 2006. © 2006 Wiley‐Liss, Inc.