- D-type cyclins (or cyclin D)* are active in the G1 phase of the cell cycle. Their expression is induced by growth factors/mitogens.
- D-type cyclins act as mitogen/growth factor sensors and link the extracellular environment to core cell cycle machinery.
- D-type cyclins have a short half-life and their degradation is regulated by ubiquitination and requires phosphorylation.
- Since mitogens/growth factors are required for the division of normal cells, cyclin D plays a critical role in the decision of cells “to divide” or “not to divide”.
- So far three members of D-type cyclins have been identified in humans: Cyclin D1, Cyclin D2, and Cyclin D3.
- D-type cyclins are the regulatory partners of Cyclin-dependent kinases CDK4 and CDK6. Together, they form holoenzymes Cyclin D-CDK4/6** which play an essential role in initiating the phosphorylation of retinoblastoma proteins (pRb, p107, and p130).
- In addition to being a regulatory partner of CDKs, D-type cyclins can also function independently of CDKs.
- Cyclin D transcription, stability, subcellular localization, and degradation are tightly controlled during cell cycle progression.
- Knockout mice lacking all three cyclins D (D1-/-, D2-/-, and D3-/-) die around mid/late gestation due to heart abnormalities and anemia.
- Cyclin D overexpression has been reported in many cancers.
* D-type cyclin or cyclin D is a term used to describe all three cyclins D1, D2, and D3.
** Cyclin D-CDK4/6 is a term used to describe all different heterodimers: Cyclin D1-CDK4, Cyclin D2-CDK4, Cyclin D3-CDK4, Cyclin D1-CDK6, Cyclin D2-CDK6, Cyclin D3-CDK6.