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PMID:17261272

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Citation

Chen, HH, Wong, YH, Geneviere, AM and Fann, MJ (2007) CDK13/CDC2L5 interacts with L-type cyclins and regulates alternative splicing. Biochem. Biophys. Res. Commun. 354:735-40

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.

Links

PubMed Online version:10.1016/j.bbrc.2007.01.049

Keywords

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

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:CCNL1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q69ZA1

F

Seeded From UniProt

complete

MOUSE:CDK13

involved_in

GO:0000380: alternative mRNA splicing, via spliceosome

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:CDK13

enables

GO:0030332: cyclin binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9JJA7

F

Seeded From UniProt

complete

MOUSE:CDK13

enables

GO:0030332: cyclin binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q52KE7

F

Seeded From UniProt

complete

MOUSE:CDK13

part_of

GO:0019908: nuclear cyclin-dependent protein kinase holoenzyme complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:CCNL2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q69ZA1

F

Seeded From UniProt

complete


See also

References

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