Cdks, cyclins and CKIs: roles beyond cell cycle regulation

Abstract

SummaryCyclin-dependent kinases (Cdks) are serine/threonine kinases and their catalytic activities are modulated by interactions with cyclins and Cdk inhibitors (CKIs). Close cooperation between this trio is necessary for ensuring orderly progression through the cell cycle. In addition to their well-established function in cell cycle control, it is becoming increasingly apparent that mammalian Cdks, cyclins and CKIs play indispensable roles in processes such as transcription, epigenetic regulation, metabolism, stem cell self-renewal, neuronal functions and spermatogenesis. Even more remarkably, they can accomplish some of these tasks individually, without the need for Cdk/cyclin complex formation or kinase activity. In this Review, we discuss the latest revelations about Cdks, cyclins and CKIs with the goal of showcasing their functional diversity beyond cell cycle regulation and their impact on development and disease in mammals.

Cell cycle S phase markers are expressed in cerebral neuron nuclei of cats infected by the Feline Panleukopenia Virus

“…Consequently, they may fulfill different functions than their known contribution to the cell cycle progress. 21,22 Polyploidy of some neurons has also been viewed as supporting the cell cycle-related neuronal death hypothesis, but physiologic neuronal polyploidy has been described. 23 In the present study, we demonstrated that S phase markers cyclin A, cdk2 and PCNA were expressed in the nuclei of neurons in brain areas were FPV proteins were produced in the cytoplasm and accumulated in the nuclei of neurons.…”

“…13 Over the last 2 decades, neuronal cell cycle re-entry, as a possible common bottle neck for most nervous system degenerative processes, has been subjected to intensive researches and controversies. [14][15][16][17][18][19][20][21][22][23] To our knowledge, this study is the first one demonstrating the existence of neuronal nuclei expressing S phase markers in the frame of a spontaneously occurring infectious disease and represents an example of inflammatory/ infectious link to the neuronal cell cycle reentry phenomenon.…”

Indole-3-carbinol (I3C) increases apoptosis, represses growth of cancer cells, and enhances adenovirus-mediated oncolysis

“…It is well established that E-type cyclins interact with the kinase CDK2 and D-type cyclins form a complex with the kinases CDK4 or CDK6 during cell proliferation. 18,19 These cyclin-CDK complexes phosphorylate retinoblastoma (Rb) protein family members, leading to E2F release from Rb and regulation of cell cycle progression from the G 1 phase into the S phase. 20 Therefore, cyclin E, cyclin D, and their related CDKs have important roles in cell proliferation.…”

CDK10 Mutations in Humans and Mice Cause Severe Growth Retardation, Spine Malformations, and Developmental Delays

“…1,2 CDKs (CDK1-CDK6) mostly promote the progression from one cell-cycle phase to the next, and CDK1 is essential for proliferation. CDKs have been characterized extensively, and some of their substrates and in vivo functions are known.…”

“…CDKs have been characterized extensively, and some of their substrates and in vivo functions are known. 1,3 Another group of CDKs, e.g., CDK7-CDK9 and CDK11-CDK13, are mostly involved in transcription. Most of the remaining CDKs are ''orphan'' kinases, which have been poorly studied.…”