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J. Biol. Chem., Vol. 276, Issue 11, 8005-8013, March 16, 2001
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and
From the Service de Biochimie et Génétique
Moléculaire, CEA/Saclay, Gif sur Yvette 91191, France
RNA polymerase II CTD kinases are key elements in
the control of mRNA synthesis. They constitute a family of
cyclin-dependent kinases activated by C-type cyclins.
Unlike most cyclin-dependent kinase complexes, which are
composed of a catalytic and a regulatory subunit, the yeast CTD kinase
I complex contains three specific subunits: a kinase subunit (Ctk1), a
cyclin subunit (Ctk2), and a third subunit (Ctk3) of unknown function
that does not exhibit any similarity to known proteins. Like the Ctk2
cyclin that is regulated at the level of protein turnover, Ctk3 is an
unstable protein processed through a ubiquitin-proteasome pathway.
Interestingly, Ctk2 and Ctk3 physical interaction is required to
protect both subunits from degradation, pointing to a new mechanism for
cyclin turnover regulation. We also show that Ctk2 and Ctk3 can each interact independently with the kinase. However, despite the formation of CDK/cyclin complexes in vitro, the Ctk2 cyclin is unable
to activate its CDK: both Ctk2 and Ctk3 are required for Ctk1 CTD kinase activation. The different specific features governing CTDK-I regulation probably reflect requirement for the transcriptional response to multiple growth conditions.
Supported by a French Ministère de la Recherche et des
Technologies fellowship and by the Association pour la Recherche contre le Cancer.
§
To whom correspondence should be addressed: Tel.: 33-1-6908-9921;
Fax: 33-1-6908-4712; E-mail: goguel@jonas.saclay.cea.fr.
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