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: 2.28). 04/2007; 354(3):735-40. DOI: 10.1016/j.bbrc.2007.01.049
Source: PubMed

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.

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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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    ABSTRACT: Eukaryotic RNA polymerase II (RNAPII) not only synthesizes mRNA but also coordinates transcription-related processes via its unique C-terminal repeat domain (CTD). The CTD is an RNAPII-specific protein segment consisting of repeating heptads with the consensus sequence Y(1)S(2)P(3)T(4)S(5)P(6)S(7) that has been shown to be extensively post-transcriptionally modified in a coordinated, but complicated, manner. Recent discoveries of new modifications, kinases, and binding proteins have challenged previously established paradigms. In this paper, we examine results and implications of recent studies related to modifications of the CTD and the respective enzymes; we also survey characterizations of new CTD-binding proteins and their associated processes and new information regarding known CTD-binding proteins. Finally, we bring into focus new results that identify two additional CTD-associated processes: nucleocytoplasmic transport of mRNA and DNA damage and repair.
    10/2011; 2011:623718. DOI:10.4061/2011/623718
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    • "Although Cdc73 is mainly a nuclear protein (Bradley et al., 2007), it has also been found in the cytoplasm, where it may interact with the actin cross-linking proteins actinin-2 and actinin-3 (Agarwal et al., 2008). Cdc2l5 belongs to a subfamily of Cdc2-related kinases (Marqués et al., 2000), and is also called the cyclindependent kinase 13 (Cdk13) due to its ability to bind to L-type cyclins (Chen et al., 2007). It has been linked to alternative splicing (Even et al., 2006), and binds, for example, to the HIV-1 Tat-protein to regulate viral mRNA splicing (Berro et al., 2008). "
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    ABSTRACT: Although a large number of actin-binding proteins and their regulators have been identified through classical approaches, gaps in our knowledge remain. Here, we used genome-wide RNA interference as a systematic method to define metazoan actin regulators based on visual phenotype. Using comparative screens in cultured Drosophila and human cells, we generated phenotypic profiles for annotated actin regulators together with proteins bearing predicted actin-binding domains. These phenotypic clusters for the known metazoan "actinome" were used to identify putative new core actin regulators, together with a number of genes with conserved but poorly studied roles in the regulation of the actin cytoskeleton, several of which we studied in detail. This work suggests that although our search for new components of the core actin machinery is nearing saturation, regulation at the level of nuclear actin export, RNA splicing, ubiquitination, and other upstream processes remains an important but unexplored frontier of actin biology.
    The Journal of Cell Biology 09/2011; 194(5):789-805. DOI:10.1083/jcb.201103168 · 9.69 Impact Factor
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    • "It was originally implicated in cholinergic signaling and cell division control in hematopoiesis (Lapidot-Lifson et al. 1992) and was named CHED (cholinesterase-related cell division controller). The rights to being called a Cdk were granted upon identification of cyclins L1 and L2 as interacting partners (Chen et al. 2007). Cdk13 also interacts with the HIV transactivator Tat and regulates viral mRNA splicing (Berro et al. 2008). "
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    ABSTRACT: The identification of new members in the Cdk and cyclin families, functions for many of which are still emerging, has added new facets to the cell cycle regulatory network. With roles extending beyond the classical regulation of cell cycle progression, these new players are involved in diverse processes such as transcription, neuronal function, and ion transport. Members closely related to Cdks and cyclins such as the Speedy/RINGO proteins offer fresh insights and hope for filling in the missing gaps in our understanding of cell division. This chapter will present a broad outlook on the cell cycle and its key regulators with special emphasis on the less-studied members and their emerging roles.
    Results and problems in cell differentiation 01/2011; 53:365-89. DOI:10.1007/978-3-642-19065-0_16

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