Orphan kinases turn eccentric A new class of cyclin Y-activated, membrane-targeted CDKs

Division of Molecular Pathophysiology
Cell cycle (Georgetown, Tex.) (Impact Factor: 4.57). 10/2012; 11(20):3758-68. DOI: 10.4161/cc.21592
Source: PubMed


PCTAIRE kinases (PCTK) are a highly conserved, but poorly characterized, subgroup of cyclin-dependent kinases (CDK). They are characterized by a conserved catalytic domain flanked by N- and C-terminal extensions that are involved in cyclin binding. Vertebrate genomes contain three highly similar PCTAIRE kinases (PCTK1,2,3, a.k.a., CDK16,17,18), which are most abundant in post-mitotic cells in brain and testis. Consistent with this restricted expression pattern, PCTK1 (CDK16) has recently been shown to be essential for spermatogenesis. PCTAIREs are activated by cyclin Y (CCNY), a highly conserved single cyclin fold protein. By binding to N-myristoylated CCNY, CDK16 is targeted to the plasma membrane. Unlike conventional cyclin-CDK interactions, binding of CCNY to CDK16 not only requires the catalytic domain, but also domains within the N-terminal extension. Interestingly, phosphorylation within this domain blocks CCNY binding, providing a novel means of cyclin-CDK regulation. By using these functional characteristics, we analyzed "PCTAIRE" sequence containing protein kinase genes in genomes of various organisms and found that CCNY and CCNY-dependent kinases are restricted to eumetazoa and possibly evolved along with development of a central nervous system. Here, we focus on the structure and regulation of PCTAIREs and discuss their established functions.

Download full-text


Available from: Johannes Rainer, Nov 05, 2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: A novel cyclin, cyclin Y, is one of the most highly conserved members of the cyclin superfamily, which is famous for their important roles in regulating the cell cycle and transcription. Recently, it was found that cyclin Y was up-regulated in many cancers. Cyclin Y may play a crucial role in tumor progression. The function and molecular mechanism of cyclin Y protein will be discussed in this paper.
    No preview · Article · Nov 2013 · Zhongguo fei ai za zhi = Chinese journal of lung cancer
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Cyclin-dependent kinases (CDKs) are protein kinases characterized by needing a separate subunit - a cyclin - that provides domains essential for enzymatic activity. CDKs play important roles in the control of cell division and modulate transcription in response to several extra- and intracellular cues. The evolutionary expansion of the CDK family in mammals led to the division of CDKs into three cell-cycle-related subfamilies (Cdk1, Cdk4 and Cdk5) and five transcriptional subfamilies (Cdk7, Cdk8, Cdk9, Cdk11 and Cdk20). Unlike the prototypical Cdc28 kinase of budding yeast, most of these CDKs bind one or a few cyclins, consistent with functional specialization during evolution. This review summarizes how, although CDKs are traditionally separated into cell-cycle or transcriptional CDKs, these activities are frequently combined in many family members. Not surprisingly, deregulation of this family of proteins is a hallmark of several diseases, including cancer, and drug-targeted inhibition of specific members has generated very encouraging results in clinical trials.
    Full-text · Article · Jun 2014 · Genome Biology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Cyclin Y is a highly conserved cyclin among eumetazoans, yet its function and regulation are poorly understood. To search for Cyclin Y-interacting proteins, we screened a yeast two-hybrid library using human Cyclin Y (CCNY) as a bait and identified the following interactors: CDK14 and four members of the 14-3-3 family (ɛ, β, η, τ). The interaction between CCNY and 14-3-3 proteins was confirmed both in vitro and in vivo. The results showed that Ser-100 and Ser-326 residues in CCNY were crucial for 14-3-3 binding. Interestingly, binding of CCNY to 14-3-3 significantly enhanced the association between CCNY and CDK14. Our findings may add a new layer of regulation of CCNY binding to its kinase partner.
    Preview · Article · Mar 2014 · Acta Biochimica et Biophysica Sinica
Show more