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

Biochem Biophys Res Commun. 2007 Mar 16;354(3):735-40. doi: 10.1016/j.bbrc.2007.01.049. Epub 2007 Jan 18.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing / genetics
  • Alternative Splicing / physiology*
  • Amino Acid Sequence
  • Blotting, Western
  • CDC2 Protein Kinase / chemistry
  • CDC2 Protein Kinase / genetics
  • CDC2 Protein Kinase / metabolism*
  • Cells, Cultured
  • Cyclins / chemistry
  • Cyclins / genetics
  • Cyclins / metabolism*
  • Humans
  • Molecular Sequence Data
  • Molecular Weight
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism

Substances

  • CCNL1 protein, human
  • Cyclins
  • RNA, Messenger
  • CDC2 Protein Kinase
  • CDK13 protein, human