Cyclin D3

Function

The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance through the cell cycle. Cyclins function as regulators of CDK kinases. Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. This cyclin forms a complex with and functions as a regulatory subunit of CDK4 or CDK6, whose activity is required for cell cycle G1/S transition. This protein has been shown to interact with and be involved in the phosphorylation of tumor suppressor protein Rb. The CDK4 activity associated with this cyclin was reported to be necessary for cell cycle progression through G2 phase into mitosis after UV radiation.

Clinical significance

Mutations in CCND3 are implicated in cases of breast cancer.

Interactions

Cyclin D3 has been shown to interact with:

• AKAP8,
• CDC2L1,
• CDKN1B,
• CRABP2,
• Cyclin-dependent kinase 4,
• Cyclin-dependent kinase 6,
• EIF3K, and
• Retinoic acid receptor alpha.

References

References

1. (July 1992). "Genomic organization, chromosomal localization, and independent expression of human cyclin D genes". Genomics.
2. "Entrez Gene: CCND3 cyclin D3".
3. (October 2012). "Comprehensive molecular portraits of human breast tumours". Nature.
4. (March 2004). "A novel partner for D-type cyclins: protein kinase A-anchoring protein AKAP95". The Biochemical Journal.
5. (September 2002). "Interaction of p58(PITSLRE), a G2/M-specific protein kinase, with cyclin D3". The Journal of Biological Chemistry.
6. (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature.
7. (April 2001). "Cdk6-cyclin D3 complex evades inhibition by inhibitor proteins and uniquely controls cell's proliferation competence". Oncogene.
8. (June 1999). "Developmentally regulated expression of cyclin D3 and its potential in vivo interacting proteins during murine gametogenesis". Endocrinology.
9. (March 1994). "Identification of G1 kinase activity for cdk6, a novel cyclin D partner". Molecular and Cellular Biology.
10. (August 2004). "Identification of the p28 subunit of eukaryotic initiation factor 3(eIF3k) as a new interaction partner of cyclin D3". FEBS Letters.
11. (February 2003). "Cyclin D3 is a cofactor of retinoic acid receptors, modulating their activity in the presence of cellular retinoic acid-binding protein II". The Journal of Biological Chemistry.