PITSLRE p110 Protein Kinases Associate with Transcription Complexes and Affect Their Activity

Trembley, Janeen H.; Hu, Dongli; Hsu, Li-Chung; Yeung, C Y; Slaughter, Clive A.; Lahti, Jill M.; Kidd, Vincent J.

doi:10.1074/jbc.m109755200

Cited by 89 publications

(96 citation statements)

References 44 publications

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“…But there was a kinase activity associated with cdk11, which later on turned out to be protein kinase CK2 (Trembley et al, 2003). Thus, this data together with the data presented here show that CK2 plays an important role in the regulation of transcription and posttranscriptional processes.…”

Section: Discussionsupporting

confidence: 72%

“…Similar to RNSP1, here we showed that an inhibition of the hPrp3p phosphorylation also leads to an inhibition of the splicing. Several proteins, which are implicated in transcription and posttranscriptional processes are substrates for protein kinase CK2 including RNA polymerase II (Payne et al, 1989), cyclin H (Schneider et al, 2002) and FCP1 (TFIIF-dependent CTD phosphatase) (Trembley et al, 2003). Interestingly, RNPS1 also interacts with the largest subunit of RNA polymerase II.…”

Section: Discussionmentioning

confidence: 99%

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Protein kinase CK2 interacts with the splicing factor hPrp3p

et al. 2007

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Numerous signalling pathways in cells are influenced by the ubiquitous Ser/Thr protein kinase CK2. Protein kinase CK2 is composed of two regulatory b-subunits and two catalytic a-or a 0 -subunits. Several of the known CK2 substrates are proteins known to regulate transcriptional events. Here, we describe that protein kinase CK2 interacts with the splicing factor hPrp3p, which is important for the assembly of the spliceosome. In a twohybrid screen hPrp3p is exclusively bound to the catalytic a-or a 0 -subunits of CK2 but not to the regulatory bsubunit. The interaction was confirmed by coimmunoprecipitation experiments in vitro and in vivo. Moreover, both proteins colocalized in nuclear speckles which is typical for splicing factor compartments within the nucleus. Phosphorylation experiments revealed that hPrp3p is also a substrate of protein kinase CK2. The main phosphorylation site was mapped to C-terminal residues. In vitro and in vivo splicing assays showed that the splicing activity is significantly influenced by the CK2-hPrp3p interaction. Thus, these data showed that CK2 is involved in the regulation of RNA processing.

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Section: Discussionsupporting

confidence: 72%

Section: Discussionmentioning

confidence: 99%

Protein kinase CK2 interacts with the splicing factor hPrp3p

et al. 2007

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“…Thus far, CDK7, CDK8, and CDK9 functions are ascribed to transcriptional initiation and elongation, and CDK12 (CrkRS) and CDK13 (CDC2L5) functions are related to pre-mRNA splicing (2)(3)(4). Interestingly, CDK11 p110 plays roles in both transcription and splicing, suggesting that this CDK may link the two processes (5,6). In addition, the CDK11 p110 partner proteins cyclins L1 and L2 also influence splicing (7,8).…”

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confidence: 99%

Characterization of Cyclin L1 and L2 Interactions with CDK11 and Splicing Factors

Loyer

Trembley

Grenet

et al. 2008

Journal of Biological Chemistry

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122

137

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Although it has been reported that cyclin L1␣ and L2␣ proteins interact with CDK11 p110 , the nature of the cyclin L transcripts, the formation of complexes between the five cyclin L and the three CDK11 protein isoforms, and the influence of these complexes on splicing have not been thoroughly investigated. Here we report that cyclin L1 and L2 genes generate 14 mRNA variants encoding six cyclin L proteins, one of which has not been described previously. Using cyclin L gene-specific antibodies, we demonstrate expression of multiple endogenous cyclin L proteins in human cell lines and mouse tissues. Moreover, we characterize interactions between CDK11 p110 , mitosis-specific CDK11 p58 , and apoptosis-specific CDK11 p46 with both cyclin L␣ and -␤ proteins and the co-elution of these proteins following size exclusion chromatography. We further establish that CDK11 p110 and associated cyclin L␣/␤ proteins localize to splicing factor compartments and nucleoplasm and interact with serine/arginine-rich proteins. Importantly, we also determine the effect of CDK11-cyclin L complexes on pre-mRNA splicing. Preincubation of nuclear extracts with purified cyclin L␣ and -␤ isoforms depletes the extract of in vitro splicing activity. Ectopic expression of cyclin L1␣, L1␤, L2␣, or L2␤ or active CDK11 p110 individually enhances intracellular intron splicing activity, whereas expression of CDK11 p58/p46 or kinase-dead CDK11 p110 represses splicing activity. Finally, we demonstrate that expression of cyclins L␣ and -␤ and CDK11 p110 strongly and differentially affects alternative splicing in vivo. Together, these data establish that CDK11 p110 interacts physically and functionally with cyclin L␣ and -␤ isoforms and SR proteins to regulate splicing.It has become apparent over the past decade that several cyclin-dependent kinases (CDKs) 4 and their cyclin regulatory partners participate in regulating mRNA production (1). Thus far, CDK7, CDK8, and CDK9 functions are ascribed to transcriptional initiation and elongation, and CDK12 (CrkRS) and CDK13 (CDC2L5) functions are related to pre-mRNA splicing (2-4). Interestingly, CDK11 p110 plays roles in both transcription and splicing, suggesting that this CDK may link the two processes (5, 6). In addition, the CDK11 p110 partner proteins cyclins L1 and L2 also influence splicing (7,8). Two distinct genes, Cdc2L1 and Cdc2L2 (acronym for Cell division control 2 Like), encode the human p110 and p58 PITSLRE protein kinases (9 -12). These kinases were renamed CDK11 p110 and CDK11 p58 when cyclins L1 and L2 were identified as regulatory subunits of CDK11 p110 (13). Expression of the CDK11 p110 isoforms is ubiquitous and constant throughout the cell cycle (11). In contrast, CDK11 p58 is expressed and functions specifically in G 2 /M via an internal ribosome entry site (IRES) located within the CDK11 p110 mRNA (14 -17). During apoptosis, a third isoform, CDK11 p46 , is generated by caspase-dependent cleavage of CDK11 p110 and CDK11 p58 , leaving the catalytic domain intact (18,19).A role for CDK11 p...

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“…Meanwhile, study of the p110 PITSLRE isoform showed that it could interact with the RNA-binding protein RNPS1, RNA polymerase II, and multiple transcriptional elongation factors, regulating some aspects of RNA splicing or transcription in proliferating cells (29,30). Thus, the identification of the cellular proteins that interact with p58 PITSLRE is a useful approach for defining the cellular function and regulatory mechanism of p58 PITSLRE .…”

mentioning

confidence: 99%

Interaction of p58PITSLRE, a G2/M-specific Protein Kinase, with Cyclin D3

Zhang¹,

Cai²,

Zhang

et al. 2002

Journal of Biological Chemistry

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The p58PITSLRE is a p34 cdc2 -related protein kinase that plays an important role in normal cell cycle progression. Elevated expression of p58 PITSLRE in eukaryotic cells prevents them from undergoing normal cytokinesis and appears to delay them in late telophase. To investigate the molecular mechanism of p58 PITSLRE action, we used the yeast two-hybrid system, screened a human fetal liver cDNA library, and identified cyclin D3 as an interacting partner of p58 PITSLRE . In vitro binding assay, in vivo coimmunoprecipitation, and immunofluorescence cell staining further confirmed the association of p58 PITSLRE with cyclin D3. This binding was observed only in the G 2 /M phase but not in the G 1 /S phase of the cell cycle; meanwhile, no interaction between p110 PITSLRE and cyclin D3 was observed in all the cell cycle. The overexpression of cyclin D3 in 7721 cells leads to an exclusively accumulation of p58 PITSLRE in the nuclear region, affecting its cellular distribution. Histone H1 kinase activity of p58 PITSLRE was greatly enhanced upon interaction with cyclin D3. Furthermore, kinase activity of p58 PITSLRE was found to increase greatly in the presence of cyclin D3 using a specific substrate, ␤-1,4-galactosyltransferase 1. These data provide a new clue to our understanding of the cellular function of p58 PITSLRE and cyclin D3.

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PITSLRE p110 Protein Kinases Associate with Transcription Complexes and Affect Their Activity

Cited by 89 publications

References 44 publications

Protein kinase CK2 interacts with the splicing factor hPrp3p

Protein kinase CK2 interacts with the splicing factor hPrp3p

Characterization of Cyclin L1 and L2 Interactions with CDK11 and Splicing Factors

Interaction of p58PITSLRE, a G2/M-specific Protein Kinase, with Cyclin D3

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