CCND1

CCND1

CCND1, also known as Cyclin D1, is a protein encoded by the CCND1 gene in humans. Cyclin D1 is a member of the highly conserved cyclin family, which is characterized by a dramatic periodicity in protein abundance throughout the cell cycle. Cyclins function as regulators of cyclin-dependent kinases (CDKs), and they are essential for the control of the cell cycle at the G1/S (start) transition.

Function

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 CCND1 gene is located on chromosome 11q13 and is frequently overexpressed in a variety of tumors, which suggests that it plays a role in oncogenesis. Overexpression of Cyclin D1 can lead to uncontrolled cell proliferation, a hallmark of cancer.

Clinical Significance

The overexpression of Cyclin D1 has been implicated in the pathogenesis of several types of cancer, including breast cancer, squamous cell carcinoma of the head and neck, and mantle cell lymphoma. In breast cancer, Cyclin D1 overexpression is associated with estrogen receptor-positive tumors and is considered a potential therapeutic target.

Regulation

Cyclin D1 expression is regulated by various signaling pathways, including the Wnt signaling pathway, PI3K/AKT pathway, and MAPK/ERK pathway. These pathways can be activated by growth factors, hormones, and other extracellular signals, leading to the transcriptional activation of the CCND1 gene.

Interactions

Cyclin D1 interacts with several proteins, including:

• CDK4 and CDK6: Cyclin D1 forms active kinase complexes with these CDKs.
• RB1: The retinoblastoma protein, which is phosphorylated by Cyclin D1/CDK4/6 complexes, leading to cell cycle progression.
• p21 and p27: Cyclin-dependent kinase inhibitors that can bind to Cyclin D1/CDK complexes and inhibit their activity.

Also see

• Cell cycle
• Cyclin-dependent kinase
• Oncogene
• Tumor suppressor gene
• Breast cancer