Cip/Kip cell-cycle inhibitors: a neuro-oncological perspective.
The cell cycle is a precisely controlled cellular program that ensures normal cellular proliferation and development. The cyclin-dependant kinases (CDK) are molecules central to the continued progression through the cell-cycle checkpoints and as such are regulated by various mechanisms including cyclin levels, phosphorylation/dephosphorylation and cyclin-dependant kinase inhibitors (CKI). The CKIs are grouped into two families based on their structure and function, four lnk4 CKIs and three Cip/Kip CKIs. Abnormalities in these proteins can give rise to developmental defects and cancer. In this review, we will discuss the biochemistry and cell biology of the each of the Cip/Kip CKIs, their role in development as evidenced by targeted mutations in mice, and their role as possible tumor suppressor genes.
Mainprize
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TG
Division of Neurosurgery and The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, University of Toronto, Canada.
Taylor
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MD
Rutka
J T
JT
Dirks
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PB
D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000502:physiology*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D050761:Cyclin-Dependent Kinase Inhibitor p57; D016213:Cyclins / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D008495:Medical Oncology / Q000379:methods; D009369:Neoplasms / Q000503:physiopathology; D009462:Neurology / Q000379:methods; D009687:Nuclear Proteins / Q000737:chemistry / Q000502:physiology*; D013329:Structure-Activity Relationship; D025521:Tumor Suppressor Proteins
C493956:CDKN1A protein, human; C493964:CDKN1C protein, human; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050761:Cyclin-Dependent Kinase Inhibitor p57; D016213:Cyclins; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27