REVIEW Functional Evolution of Cyclin-Dependent Kinases John H. Doonan ® Georgios Kitsios Ó Humana Press 2008 Abstract Cyclin-dependent kinases (CDKs) are serine/ threonine protein kinases with a well established role in the regulation of the eukaryotic cell cycle. Recent studies with animal cells have implicated CDK activity in additional diverse cellular processes, including transcription, transla- tion and mRNA processing. In plants, such CDK functions are poorly characterized and the implication of CDK phosphorylation in regulation of gene expression is just begining to emerge. In this review we compare CDK functions in plants, animals and yeasts with particular focus on the biological processes that different members parti- cipate in and regulate. Finally, based on the available information of CDK function, we propose an alternative evolutionary scenario for the CDK gene family. Keywords Cyclin-dependent kinases Á Cell cycle Á Gene expression Á Plant Á Animal Á Yeast Introduction Cyclin-dependent kinases (CDKs) are a large and impor- tant family of serine/threonine protein kinases that have diverse regulatory roles in a number of cellular and developmental processes in eukaryotes. The defining fea- ture for the family was a requirement that founding members had for an activating subunit called cyclin. Cyclins were so-called because the prototypical cell cycle cyclins varied in abundance cyclically during the cell cycle [1]. Cyclins, in general, function as regulatory subunits of the CDK–cyclin complexes and, in most cases, the kinase catalytic subunit has little activity on its own. As new CDKs have been discovered, so have new cyclins and many of these are relative stable proteins that do not cycle. In a few cases, the novel CDKs do not require any cyclin partner for activity. Although first identified as having a central role in cell cycle progression, the ever enlarging families of CDK and cyclin proteins have been implicated in a diverse and somewhat bewildering array of processes. In this review, we discuss the roles of eukaryotic CDKs and highlight differences and similarities, in terms of protein family organization and biological functions, between plant and animal counterparts. We speculate that the prototypical kinases, evolved to control cell division in complex multi- compartmentalized eukaryotic cells, were generalist kina- ses that had truly global effects on cellular structure, gene expression and metabolism: however, as the family diver- sified during eukaryotic evolution, many of the more recent members became specialized, taking up more specialist roles regulating particular aspects of gene expression. A Brief History of CDKs CDKs were first ‘‘discovered’’ when a kinase activity was shown to be the active component of mitosis-promoting factor (MPF), an autocatalytic proteinaceous factor that could drive an interphase cell into mitosis [2]. During the same period, genetic studies of yeast cell division cycle mutants defined cdc2/CDC28 as master regulators of cell J. H. Doonan (&) Department of Cell & Developmental Biology, John Innes Centre, Colney Lane, Norwich NR4 7UH, UK e-mail: john.doonan@bbsrc.ac.uk G. Kitsios Department of Agricultural Biotechnology, Agricultural University of Athens, Iera Odos 75, 11855 Athens, Greece e-mail: gkitsios@aua.gr Mol Biotechnol DOI 10.1007/s12033-008-9126-8