Phylogenetic analysis of CDK and cyclin proteins in premetazoan lineages

Abstract

BackgroundThe molecular history of animal evolution from single-celled ancestors remains a major question in biology, and little is known regarding the evolution of cell cycle regulation during animal emergence. In this study, we conducted a comprehensive evolutionary analysis of CDK and cyclin proteins in metazoans and their unicellular relatives.ResultsOur analysis divided the CDK family into eight subfamilies. Seven subfamilies (CDK1/2/3, CDK5, CDK7, CDK 20, CDK8/19, CDK9, and CDK10/11) are conserved in metazoans and fungi, with the remaining subfamily, CDK4/6, found only in eumetazoans. With respect to cyclins, cyclin C, H, L, Y subfamilies, and cyclin K and T as a whole subfamily, are generally conserved in animal, fungi, and amoeba Dictyostelium discoideum. In contrast, cyclin subfamilies B, A, E, and D, which are cell cycle-related, have distinct evolutionary histories. The cyclin B subfamily is generally conserved in D. discoideum, fungi, and animals, whereas cyclin A and E subfamilies are both present in animals and their unicellular relatives such as choanoflagellate Monosiga brevicollis and filasterean Capsaspora owczarzaki, but are absent in fungi and D. discoideum. Although absent in fungi and D. discoideum, cyclin D subfamily orthologs can be found in the early-emerging, non-opisthokont apusozoan Thecamonas trahens. Within opisthokonta, the cyclin D subfamily is conserved only in eumetazoans, and is absent in fungi, choanoflagellates, and the basal metazoan Amphimedon queenslandica.ConclusionsOur data indicate that the CDK4/6 subfamily and eumetazoans emerged simultaneously, with the evolutionary conservation of the cyclin D subfamily also tightly linked with eumetazoan appearance. Establishment of the CDK4/6-cyclin D complex may have been the key step in the evolution of cell cycle control during eumetazoan emergence.

Shear force-based genetic screen reveals negative regulators of cell adhesion and protrusive activity

“…Moreover, Dictyostelium pten-cells do not display the increased proliferation rates seen in mammalian cells lacking this gene, which would complicate the screen. It appears that Dictyostelium cells do not possess PIP3-dependent cell cycle checkpoints as in animal cells (19,21,22). We reasoned that other negative regulators in signaling or cytoskeletal pathways would lead to a similar phenotype as seen in pten-cells consisting of increased protrusive activity, cell spreading, contact area, and substrate adhesion.…”

Legionella pneumophila prevents proliferation of its natural host Acanthamoeba castellanii

“…Because Homo sapiens cells possess a considerable number of CDKs, we ran a blast search of protein sequences of human CDKs (supplementary Data 1)18 within the genome of A. castellanii (NCBI). Based on an E-value less than 1 and a percentage of identity of at least 35%, we obtained five candidates as putative CDKs of A. castellanii (Table 1).…”

Targeting CDK6 in cancer: State of the art and new insights

“…To date, at least 20 CDKs and 30 cyclins have been reported. 1,2 Among them, CDK1, CDK2, CDK4 and CDK6 regulate the transition of phases in the cell cycle while CDKs 7-11 are involved in transcription. 3 CDK6 gene is located in human chromosome 7 and is translated into a kinase with 326 amino acids.…”