Characterization of a novel human CDK5 splicing variant that inhibits Wnt/beta-catenin signaling.

The cyclin-dependent kinases (CDKs) are a family of serine/threonine kinases, playing an essential role in regulating cell-cycle progression. In our present work, human CDK5 and a novel CDK5 splicing variant, named as CDK5-SV, were cloned from the cDNA library of human testis. CDK5-SV lacking the exon 7 of CDK5 encodes a protein of 260 amino acids. Through RT-PCR analysis in different human tissues, CDK5-SV was found to be expressed in testis, skeletal muscle, colon, bone marrow and ovary, while CDK5 was ubiquitously expressed. Immunofluorescence experiment in HeLa cells showed that the subcellular localizations of CDK5-SV and CDK5 were totally different. CDK5 mainly located in the cytoplasm, while CDK5-SV accumulated in nucleus. Reporter gene assay showed that when co-transfected with beta-catenin, CDK5 and CDK5-SV could both strongly inhibit the Wnt/beta-catenin signaling pathway. Consistently, CDK5-SV could also interact with beta-catenin as CDK5 does. Taken together, our findings suggest that CDK5-SV might also be a negative regulator of Wnt/beta-catenin signaling pathway.