CDK13/CDC2L5 interacts with L-type cyclins and regulates alternative splicing

School of Life Sciences, National Yang Ming University, T’ai-pei, Taipei, Taiwan
Biochemical and Biophysical Research Communications (Impact Factor: 2.3). 04/2007; 354(3):735-40. DOI: 10.1016/j.bbrc.2007.01.049
Source: PubMed


Due to the strong sequence homology it has been suggested that CDC2L5 and CDK12 belong to a high molecular weight subfamily of CDC2 family with PITAI/VRE motifs [F. Marques, J.L. Moreau, G. Peaucellier, J.C. Lozano, P. Schatt, A. Picard, I. Callebaut, E. Perret, A.M. Geneviere, A new subfamily of high molecular mass CDC2-related kinases with PITAI/VRE motifs, Biochem. Biophys. Res. Commun. 279 (2000) 832-837]. Recently, we reported that CDK12 interacts with L-type cyclins and is involved in alternative splicing regulation [H.-H. Chen, Y.-C. Wang, M.-J. Fann, Identification and characterization of the CDK12/Cyclin L1 complex involved in alternative splicing regulation, Mol. Cel. Biol. 26 (2006) 2736-2745]. Here, we provide evidence that CDC2L5 also interacts with L-type cyclins and thus rename it as cyclin-dependent kinase 13 (CDK13). The kinase domain of CDK13 is sufficient to bind the cyclin domains of L-type cyclins. Moreover, CDK13 and L-type cyclins modulate each other's subcellular localization. When CDK13 and an E1a minigene reporter construct were over-expressed in HEK293T cells, CDK13 alters the splicing pattern of E1a transcripts in a dose-dependent manner. Similar to effects of CDK12, effects of CDK13 on splicing pattern are counteracted by SF2/ASF and SC35. These findings strengthen CDK12 and CDK13 as a subfamily of cyclin-dependent kinases that regulate alternative splicing.

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    • "These heterodimers are both implicated in the control of RNA-pol-II-mediated transcription [42–44]. CDK12 and CDK13 may also associate with L-type cyclins and take part in the regulation of alternative RNA splicing [45, 46]. "
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    • "Cdk12 was shown to phosphorylate CTD of RNAPII, in vitro [25]. Based on the interaction of Cdk12 and Cdk13 with overexpressed Cyclin L (CycL), CycL was reported to be their regulatory subunit, and the same studies suggested a role in the regulation of alternative splicing [28,29]. However, recent studies have reported that the endogenous Drosophila Cdk12 and human Cdk12 and Cdk13 do not associate with CycL, but rather with CycK [5,6]. "
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    • "In terms of the cyclin partner of CDK12, our lab found that endogenous dCDK12 associates with cyclinK, a Ctk2-like cyclin that has been previously characterized as an alternative partner for CDK9 [78]. These findings are inconsistent with previous reports that CDK12 and CDK13 interact with the L class cyclins [74] [75]; thus, whether cyclinK is the cyclin partner of human CDK12 and CDK13 remains to be determined. As of this paper, other than our initial characterization, there have been no published studies of CDK12 and CDK13 in the context of transcription and transcriptional elongation, thus much remains to be learned about these kinases. "
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