Cyclin D1 (synonymes: PRAD1, parathyroid adenomatosis 1, CCND1) is a 295 amino acid protein, 36 kDa, which belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance throughout the cell cycle. Cyclin D1 forms a complex with and functions as a regulatory subunit of CDK4 or CDK6, whose activity is required for cell cycle G1/S transition. The protein has been shown to interact with tumour suppressor protein Rb and its expression is regulated positively by Rb.
The expression is cell cycle dependant, maximal in G1 and minimal in S phase. Localization is mainly nuclear. In normal tissues, Cyclin D1 expression is restricted to the proliferative zone of epithelial tissues, endothelium and some fibroblasts. There is no expression in lymphoid tissue.
Mutations with amplification of the cyclin D1 gene, with overexpression of the protein, which alters cell cycle progression, are observed frequently in a variety of tumours and may contribute to tumourigenesis.
In diagnostic pathology, immunohistochemical detection of Cyclin D1 is used mainly for the diagnosis of mantle cell lymphoma. While other methods of cyclin D1 detection are being explored, immunohistochemistry is still widely used and anti-cyclin D1 antibodies remain an essential component in a small B-cell lymphoproliferative disorder panel.
Mantle cell lymphoma
Synthetic peptide corresponding to residues within aa200-295 of Cyclin D1 was used as an immunogen.
1.Hirai, H. et al. Novel INK4 proteins, p19 and p18, are specific inhibitors of the cyclin D-dependent kinases CDK4 and CDK6. Mol Cell Biol. 1995 May; 15(5): 2672–2681.
2.Sherr, C.J. Cancer cell cycles. Science. 1996 Dec 6;274(5293):1672-7.