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Query: EC:2.7.7.6 (
RNA polymerase
)
34,946
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The PITSLRE protein kinases, hereafter referred to as
CDK11
because of their association with the cyclin L regulatory partner, belong to large molecular weight protein complexes that contain
RNA polymerase II
. These
CDK11
(p110) complexes have been reported to influence transcription as well as interact with the general pre-mRNA-splicing factor RNPS1. Some of these complexes may also play a role in pre-mRNA splicing. Using a two-hybrid interactive screen, the splicing protein 9G8 was identified as an in vivo partner for
CDK11
(p110). The identification of several splicing-related factors as
CDK11
(p110) interactors along with the close relationship between transcription and splicing indicated that
CDK11
(p110) might influence splicing activity directly. Immunodepletion of
CDK11
(p110) from splicing extracts greatly reduced the appearance of spliced products using an in vitro assay system. Moreover, the re-addition of these
CDK11
(p110) immune complexes to the
CDK11
(p110)-immunodepleted splicing reactions completely restored splicing activity. Similarly, the addition of purified
CDK11
(p110) amino-terminal domain protein was sufficient to inhibit the splicing reaction. Finally, 9G8 is a phosphoprotein in vivo and is a substrate for
CDK11
(p110) phosphorylation in vitro. These data are among the first demonstrations showing that a CDK activity is functionally coupled to the regulation of pre-mRNA-splicing events and further support the hypothesis that
CDK11
(p110) is in a signaling pathway that may help to coordinate transcription and RNA-processing events.
...
PMID:CDK11 complexes promote pre-mRNA splicing. 1250 Dec 47
Cyclin-dependent kinase (CDK)11(p110), formerly known as PITSLRE, is a serine/threonine kinase whose catalytic activity has been associated with transcription and RNA processing. To further evaluate the regulation of
CDK11
(p110) catalytic activity, interacting proteins were identified by liquid chromatography and tandem mass spectrometry (LC-MS/MS). Following the immunoprecipitation of
CDK11
(p110) from COS-7 cells, the serine/threonine kinase CK2 was identified by LC-MS/MS. These results were extended through the observation that
CDK11
(p110) serves as a substrate for CK2 and the identification of a phosphorylation site on
CDK11
(p110) at Ser227 by LC-MS/MS. To obtain
CDK11
(p110) devoid of CK2,
CDK11
(p110) was expressed in High Five insect cells and secreted into the media due to the presence of a honeybee melittin signal sequence encoded at the amino-terminus of
CDK11
(p110). Recombinant
CDK11
(p110) was purified from the media and phosphorylation of histone H1 subsequently demonstrated. After demonstrating retention of
CDK11
(p110) kinase activity, it was evaluated for activity on the carboxyl-terminal domain (CTD) of the largest subunit of
RNA polymerase II
(RNAP II), but only CK2 was found to phosphorylate the CTD.
...
PMID:Cyclin-dependent kinase 11(p110) activity in the absence of CK2. 1464 19
The
CDK11
(p110) protein kinases are part of large-molecular-weight complexes that also contain
RNA polymerase II
, transcriptional elongation factors, and general pre-mRNA splicing factors.
CDK11
(p110) isoforms may therefore couple transcription and pre-mRNA splicing by their effect(s) on certain proteins required for these processes. The
CDK11
(p58) kinase isoform is generated from the
CDK11
(p110) mRNA through the use of an internal ribosome entry site in a mitosis-specific manner, suggesting that this kinase may regulate the cell cycle during mitosis. The in vivo role and necessity of
CDK11
(p110/p58) kinase function during mammalian development were examined by generating
CDK11
(p110/p58)-null mice through targeted disruption of the corresponding gene using homologous recombination. While heterozygous mice develop normally, disruption of both
CDK11
(p110/p58) alleles results in early embryonic lethality due to apoptosis of the blastocyst cells between 3.5 and 4 days postcoitus. Cells within these embryos exhibit both proliferative defect(s) and a mitotic arrest. These results are consistent with the proposed cellular functions of the
CDK11
(p110/p58) kinases and confirm that the
CDK11
(p110/p58) kinases are essential for cellular viability as well as normal early embryonic development.
...
PMID:Failure to proliferate and mitotic arrest of CDK11(p110/p58)-null mutant mice at the blastocyst stage of embryonic cell development. 1506 Jan 43
The Mediator is a multiprotein transcriptional coactivator that is expressed ubiquitously in eukaryotes from yeast to mammals and is required for induction of
RNA polymerase II
(pol II) transcription by DNA binding transcription factors. In the work described here, we exploit multidimensional protein identification technology (MudPIT) to carry out a proteomic analysis of the subunit composition of the mammalian Mediator complex. By comparing MudPIT data sets obtained from six independent Mediator preparations immunoaffinity purified through their Nut2 (MED10), Med25 (MED9), Intersex (MED29), LCMR1 (MED19), AK007855 (MED28), or CRSP70 (MED26) subunits, we identify a set of consensus mammalian Mediator subunits. In addition, we identify as Mediator-associated proteins the CDK8-like cyclin-dependent kinase
CDK11
and the TRAP240-like KIAA1025 protein (MED13L), which is mutated in patients with the congenital heart defect transposition of the great arteries (TGA).
...
PMID:A set of consensus mammalian mediator subunits identified by multidimensional protein identification technology. 1517 63
Mediator is an essential transcriptional cofactor of
RNA polymerase II
(Pol II) in eukaryotes. This cofactor is a large complex containing up to 30 subunits and consisting of four modules: head, middle, tail, and CDK/Cyclin. Generally, Mediator connects transcriptional regulators, cofactors, chromatin regulators, and chromatin remodellers, with the pre-initiation complex to provide a platform for the assembly of these factors. Many previous studies have revealed that CDK8, a subunit of the CDK/Cyclin module, is one of the key subunits mediating the pivotal roles of Mediator in transcriptional regulation. In addition to CDK8,
CDK11
is conserved among vertebrates as a Mediator subunit and closely resembles CDK8. While the role of CDK8 has been studied extensively, little is known of the role of
CDK11
in Mediator. We purified human
CDK11
(hCDK11)-containing protein complexes from an epitope-tagged hCDK11-expressing HeLa cell line and found that hCDK11 could independently form Mediator complexes devoid of human CDK8 (hCDK8). To investigate the in vivo transcriptional activity of the complex, we employed a luciferase assay. Although hCDK11 has nearly 80% amino acid sequence identity to hCDK8, siRNA-knockdown study revealed that hCDK8 and hCDK11 possess opposing functions in viral activator VP16-dependent transcriptional regulation.
...
PMID:Human mediator kinase subunit CDK11 plays a negative role in viral activator VP16-dependent transcriptional regulation. 1865 50
In eukaryotes, cyclin-dependent kinases (CDKs) control the cell cycle and critical steps in gene expression. The lethal parasite Trypanosoma brucei, member of the phylogenetic order Kinetoplastida, possesses eleven CDKs which, due to high sequence divergence, were generically termed CDC2-related kinases (CRKs). While several CRKs have been implied in the cell cycle, CRK9 was the first trypanosome CDK shown to control the unusual mode of gene expression found in kinetoplastids. In these organisms, protein-coding genes are arranged in tandem arrays which are transcribed polycistronically. Individual mRNAs are processed from precursor RNA by spliced leader (SL) trans splicing and polyadenylation. CRK9 ablation was lethal in cultured trypanosomes, causing a block of trans splicing before the first transesterification step. Additionally, CRK9 silencing led to dephosphorylation of
RNA polymerase II
and to hypomethylation of the SL cap structure. Here, we tandem affinity-purified CRK9 and, among potential CRK9 substrates and modifying enzymes, discovered an unusual tripartite complex comprising CRK9, a new L-type cyclin (CYC12) and a protein, termed CRK9-associated protein (CRK9AP), that is only conserved among kinetoplastids. Silencing of either CYC12 or CRK9AP reproduced the effects of depleting CRK9, identifying these proteins as functional partners of CRK9 in vivo. While mammalian cyclin L binds to
CDK11
, the CRK9 complex deviates substantially from that of
CDK11
, requiring CRK9AP for efficient CRK9 complex formation and autophosphorylation in vitro. Interference with this unusual CDK rescued mice from lethal trypanosome infections, validating CRK9 as a potential chemotherapeutic target.
...
PMID:Cyclin-Dependent Kinase CRK9, Required for Spliced Leader trans Splicing of Pre-mRNA in Trypanosomes, Functions in a Complex with a New L-Type Cyclin and a Kinetoplastid-Specific Protein. 2695 83
