Loss of cks1 homeostasis deregulates cell division cycle.
Genetic and biochemical studies have provided considerable insight into the multiple functions of cyclin-dependent kinase subunit (cks)1 in cell division cycle. In addition to enhanced substrate targeting by specific ubiquitin ligases SCF(skp2) and APC/C, its direct interaction with proteasome components normalizes multiple cell cycle regulators. Importantly, it also acts as a transcriptional regulator. cks1 overexpression reflects poor prognosis in malignancy thus indicating its possible role in tumour diagnosis and management. The present review compiles the multiple functional roles of cks1 in cell division with specific emphasis on its molecular mechanisms. Its docking functions and the possible downstream proteolytic and transcriptional targets are described. The spatial configuration of cks1-cdk2 complex and the structural organization of cks1-p27-skp2 assembly required for p27 ubiquitination are discussed in detail. In addition to enhanced p27 degradation, the possible other mechanisms which underlie its pathological functions in human cancer progression are also discussed. Though there are apparent gaps in information, the turnover mechanism of cks1 is well addressed and presents opportunity to exploit the target for disease management.
Krishnan
Anand
A
Translational Cancer Research Laboratory, Department of Molecular Medicine, Rajiv Gandhi Centre for Biotechnology, Kerala, India.
Nair
S Asha
SA
Pillai
M Radhakrishna
MR
D000818:Animals; D042846:CDC2-CDC28 Kinases; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology*; D051357:Cyclin-Dependent Kinase 2 / Q000235:genetics / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism*; D018450:Disease Progression; D004789:Enzyme Activation; D006706:Homeostasis; D006801:Humans; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D011485:Protein Binding; D044786:S-Phase Kinase-Associated Proteins / Q000378:metabolism; D014158:Transcription, Genetic; D054875:Ubiquitination
C093090:CKS1B protein, human; D002352:Carrier Proteins; D044786:S-Phase Kinase-Associated Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases