Cyclin Dependent Kinase 11 in RNA Transcription and Splicing

Trembley, Janeen H.; Loyer, Pascal; Hu, Dongli; Li, Tongyuan; Grenet, José; Lahti, Jill M.; Kidd, Vincent J.

doi:10.1016/s0079-6603(04)77007-5

Cited by 48 publications

(65 citation statements)

References 81 publications

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“…Antibodies-The CDK11 antibodies P2N100 and P1C have been described previously (12,24). The cyclin L antibodies were produced by immunization of rabbits with purified His 6 -tagged full-length cyclin L1␤ (pan-L antibody), His 6 -tagged cyclin L1␣ peptide (cyclin L1␣-specific antibody, amino acids 314 -369), or GST-cyclin L2␣ peptide (cyclin L2␣-specific antibody, amino acids 307-379).…”

Section: Methodsmentioning

confidence: 99%

“…Faster migrating signals, which possibly represent proteolytic fragments of cyclins L1␣ and L2␣, were also detected in various fractions of HeLa NE (8 -11, 15-17); however, we have not further characterized these bands. The two cyclin L␣ isoforms were also detected in mouse liver although in slightly smaller sized protein complex fractions (12)(13)(14)(15)(16). In addition, immunoblot analysis using the pan-L antibody allowed detection of cyclin L␤ proteins in mouse liver fractions 16 -20, corresponding to molecular masses of approximately Ͻ25-120 kDa.…”

Section: Table 2 Summary Of Cdk11 and Cyclin L1/2 Co-immunoprecipitatmentioning

confidence: 98%

“…8A) that encodes unspliced and five alternatively spliced variant transcripts (13,12,11,10, and 9S) was employed to investigate whether ectopic expression of wild-type (WT) and kinase-dead (DN) forms of CDK11 p110 and cyclins L1␣, L2␣, and L2␤ (those isoforms that interact with CDK11 p110 ) affects alternative splicing activity in HuH7 hepatoma cells. In these experiments, total RNA was extracted from HuH7 cells following transient transfection with the E1A minigene and CDK11 p110 and cyclin L expression vectors.…”

Section: Expression Of Cyclin L1/2 Isoforms Alone or In Combination Wmentioning

confidence: 99%

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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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120

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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Section: Methodsmentioning

confidence: 99%

Section: Table 2 Summary Of Cdk11 and Cyclin L1/2 Co-immunoprecipitatmentioning

confidence: 98%

Section: Expression Of Cyclin L1/2 Isoforms Alone or In Combination Wmentioning

confidence: 99%

See 1 more Smart Citation

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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120

137

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“…Cyclin-dependent kinases (CDKs) are involved in a variety of important regulatory pathways in eukaryotic cells, including cell-cycle control, apoptosis, neuronal physiology, differentiation and transcription (Harper and Adams, 2001;Trembley et al, 2004;Chen et al, 2006). The human (CDC2L1 and CDC2L2) and mouse (cdc21) genes both produce two different protein products.…”

Section: Introductionmentioning

confidence: 99%

CDK11p58 is required for the maintenance of sister chromatid cohesion

Valentine

Kidd

et al. 2007

Journal of Cell Science

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“…Recently, the Cdk11 p58 protein kinase was also shown to be essential for mitosis (Hu et al, 2007;Petretti et al, 2006). In humans, the Cell division control 2 Like genes Cdc2L1 and Cdc2L2 encode two related protein kinases, denoted Cdk11B and A, respectively, which are expressed as two predominant protein isoforms designated by their apparent molecular weight of 110 and 58kDa for the Cdk11 p110A/B and Cdk11 p58A/B isoforms, respectively (Trembley et al, 2004). The CDK11 p110 and CDK11 p58 isoforms are produced from the same mRNAs through the use of an internal ribosome entry site (IRES) and two different AUG codons located in the coding sequence of the CDK11 p110 A and B mRNAs.…”

Section: Sequential Activation Of Cdk/cyclin Complexes During the Celmentioning

confidence: 99%

Regulation of the G1/S Transition in Adult Liver: Expression and Activation of the Cyclin Dependent Kinase Cdk1 in Differentiated Hepatocytes is Controlled by Extracellular Signals and is Crucial for Commitment to DNA Replication

Loyer¹,

Corlu²

2011

DNA Replication-Current Advances

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Cyclin Dependent Kinase 11 in RNA Transcription and Splicing

Cited by 48 publications

References 81 publications

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

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

CDK11p58 is required for the maintenance of sister chromatid cohesion

Regulation of the G1/S Transition in Adult Liver: Expression and Activation of the Cyclin Dependent Kinase Cdk1 in Differentiated Hepatocytes is Controlled by Extracellular Signals and is Crucial for Commitment to DNA Replication

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