Regulators of G1 cyclin-dependent kinases and cancers

Cancer Metastasis Rev. 2003 Dec;22(4):435-49. doi: 10.1023/a:1023785332315.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • CDC2-CDC28 Kinases / metabolism
  • Cyclin E / metabolism
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinases / metabolism
  • Cyclin-Dependent Kinases / physiology*
  • Disease Progression
  • G1 Phase*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Models, Biological
  • Neoplasms / enzymology*
  • Neoplasms / metabolism
  • Proto-Oncogene Proteins*


  • Cyclin E
  • Proto-Oncogene Proteins
  • CDC2-CDC28 Kinases
  • CDK2 protein, human
  • CDK4 protein, human
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinases