Identification of human cyclin-dependent kinase 8, a putative protein kinase partner for cyclin C
J P Tassan1, M Jaquenoud, P Léopold
1Swiss Institute for Experimental Cancer Research (ISREC), Epalinges.
Abstract:
Metazoan cyclin C was originally isolated by virtue of its ability to rescue Saccharomyces cerevisiae cells deficient in G1 cyclin function. This suggested that cyclin C might play a role in cell cycle control, but progress toward understanding the function of this cyclin has been hampered by the lack of information on a potential kinase partner. Here we report the identification of a human protein kinase, K35 [cyclin-dependent kinase 8 (CDK8)], that is likely to be a physiological partner of cyclin C. A specific interaction between K35 and cyclin C could be demonstrated after translation of CDKs and cyclins in vitro. Furthermore, cyclin C could be detected in K35 immunoprecipitates prepared from HeLa cells, indicating that the two proteins form a complex also in vivo. The K35-cyclin C complex is structurally related to SRB10-SRB11, a CDK-cyclin pair recently shown to be part of the RNA polymerase II holoenzyme of S. cerevisiae. Hence, we propose that human K35(CDK8)-cyclin C might be functionally associated with the mammalian transcription apparatus, perhaps involved in relaying growth-regulatory signals.
Insights
Researchers identified a human protein kinase, K35 (cyclin-dependent kinase 8 or CDK8), as a likely partner for cyclin C. This cyclin C-CDK8 complex may associate with the mammalian transcription apparatus, potentially relaying growth signals.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Metazoan cyclin C was initially identified for its role in rescuing yeast cell cycle deficiencies.
- Understanding cyclin C's function was limited by the absence of its kinase partner.
- Previous research suggested a potential role for cyclin C in cell cycle control.
Purpose of the Study:
- To identify the physiological kinase partner of human cyclin C.
- To investigate the interaction between cyclin C and its potential kinase partner.
- To explore the functional association of the cyclin C-kinase complex in mammalian cells.
Main Methods:
- In vitro translation of cyclin-dependent kinases (CDKs) and cyclins to demonstrate specific interactions.
- Immunoprecipitation of K35 (CDK8) from HeLa cell extracts to detect associated cyclin C.
- Structural and functional comparisons with the yeast SRB10-SRB11 CDK-cyclin pair.
Main Results:
- A human protein kinase, K35 (CDK8), was identified as a likely physiological partner of cyclin C.
- Specific in vitro interactions between K35 and cyclin C were demonstrated.
- Cyclin C was detected in K35 immunoprecipitates from HeLa cells, confirming in vivo complex formation.
- The K35-cyclin C complex shows structural similarity to the yeast SRB10-SRB11 complex.
Conclusions:
- Human K35 (CDK8) and cyclin C form a complex in vivo.
- This complex is structurally related to a component of the yeast RNA polymerase II holoenzyme.
- The K35-cyclin C complex is proposed to be functionally associated with the mammalian transcription apparatus.
- This association may play a role in relaying growth-regulatory signals.
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