Regulators of G1 cyclin-dependent kinases and cancers.
The mammalian cell cycle can be divided into four phases: G1 (gap phase 1), S (DNA synthesis), G2 (gap phase 2), and M (mitosis). Progression through each phase of the cell cycle is delicately controled by the activity of different cyclin-dependent kinases (CDKs) and their regulatory subunits known as cyclins. CDK2, CDK4, CDK6 and their associated cyclins control the G1 to S phase transition. The association of CDK4 or CDK6 with D-type cyclins is critical for G1 phase progression, whereas the CDK2-cyclin E complex is important for initiation of the S phase. Cancer can originate from dysregulation of these regulators. A variety of intrinsic and extrinsic signals were recently identified to regulate these G1 or G1/S CDKs and cyclins. Here we discuss the regulators of these protein kinases at different mechanistic level with a hope that these insights can be applied to develop therapeutic strategies for cancer treatment.
Lee
Mong-Hong
MH
Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA. mhlee@notes.mdacc.tmc.edu
Yang
Heng-Yin
HY
D042846:CDC2-CDC28 Kinases / Q000378:metabolism; D019927:Cyclin E / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases / Q000378:metabolism / Q000502:physiology*; D018450:Disease Progression; D016193:G1 Phase; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000201:enzymology* / Q000378:metabolism; D011518:Proto-Oncogene Proteins
D019927:Cyclin E; D011518:Proto-Oncogene Proteins; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; C495900:CDK4 protein, human; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases