Cyclin D is a member of the cyclin family, and comprises three closely related proteins, cyclin D1, D2 and D3. These are expressed in an overlapping, redundant fashion in all proliferating cell types and collectively control the progression of cells through the cell cycle. Since the D-cyclins are essential to cell division, they are also dysregulated in cancer.
Cyclin D1
Cyclin D1 belongs to the family of cyclin proteins which function as the regulatory subunits of cyclin/cyclin dependent kinase (Cdk) holoenzymes that regulate entry into and progression through the cell cycle. Cyclin D1 expression is induced upon stimulation by growth factors (e.g.EGF, IGF-I/II), amino acids, hormones, and oncogenes such as Ras, Src, ErbB2, and SV40 T antigen. Cdk4 and Cdk6 can partner with Cyclin D1 in early to mid-G1 phase to phosphorylate and inactivate the cell-cycle inhibitory function of the retinoblastoma protein (pRB) in cooperation with Cyclin E/Cdk2. Cyclin D1 is also known to modulate local chromatin structure and transcription of genes involved in proliferation and differentiation through CDK-independent association with histone acetylases (e.g. CBP, P/CAF) and deacetylases. Amplification or overexpression of Cyclin D1 is important in the development of many cancers including parathyroid adenoma,breast,prostate and colon cancers,lymphoma and melanoma.
Encyclopedia
top
