CDKN2C

CDKN2C is a gene that plays a crucial role in regulating cell cycle progression and cell growth. It is also known as cyclin-dependent kinase inhibitor 2C. In this article, we will explore the various aspects of CDKN2C, including its function, structure, and significance in human health.

Function

CDKN2C is a tumor suppressor gene that encodes a protein called p18INK4C. This protein belongs to the INK4 family of cyclin-dependent kinase inhibitors, which are responsible for inhibiting the activity of cyclin-dependent kinases (CDKs). CDKs are enzymes that regulate the progression of the cell cycle by phosphorylating target proteins.

The p18INK4C protein specifically inhibits the activity of CDK4 and CDK6, which are involved in the G1 phase of the cell cycle. By inhibiting these CDKs, p18INK4C prevents the phosphorylation of the retinoblastoma protein (RB), thereby preventing the progression of the cell cycle from G1 to S phase. This inhibition helps to maintain proper cell cycle control and prevents uncontrolled cell growth.

Structure

The CDKN2C gene is located on chromosome 1p32.3 and consists of three exons. The protein encoded by this gene, p18INK4C, is composed of 166 amino acids. It contains four ankyrin repeats, which are structural motifs involved in protein-protein interactions.

The ankyrin repeats in p18INK4C are responsible for its binding to CDK4 and CDK6. By binding to these CDKs, p18INK4C blocks their interaction with cyclin D, preventing the formation of active CDK-cyclin complexes. This binding interaction is crucial for the inhibitory function of p18INK4C.

Significance

CDKN2C is considered a tumor suppressor gene due to its role in regulating cell cycle progression. Mutations or deletions in this gene can lead to the loss of p18INK4C function, resulting in uncontrolled cell growth and an increased risk of cancer development.

Studies have shown that CDKN2C is frequently altered in various types of cancer, including lung cancer, breast cancer, and melanoma. These alterations can occur through genetic mutations, epigenetic modifications, or chromosomal deletions. Loss of CDKN2C function allows CDK4 and CDK6 to become overactive, leading to uncontrolled cell proliferation and tumor formation.

Clinical Implications

The dysregulation of CDKN2C has important clinical implications. It has been suggested that CDKN2C alterations could serve as potential biomarkers for cancer diagnosis, prognosis, and treatment response. Understanding the molecular mechanisms underlying CDKN2C dysfunction may help in the development of targeted therapies for cancers with CDKN2C alterations.

See Also

• Cyclin-dependent kinase
• Tumor suppressor gene
• Cell cycle
• Retinoblastoma protein

References

1. Zhang J, et al. (2019). CDKN2C/INK4C loss: a novel prognostic biomarker in localized and metastatic clear cell renal cell carcinoma. Sci Rep. 9(1):3267. 2. Sherr CJ, et al. (1996). The INK4a/ARF network in tumour suppression. Nat Rev Mol Cell Biol. 2(10):731-7. 3. Koh J, et al. (2019). CDKN2C loss is associated with adverse prognosis in head and neck squamous cell carcinoma. Sci Rep. 9(1):18104. Template:Gene-stub