p16CDKN2A

The p16INK4a gene, also known as CDKN2A (Cyclin-Dependent Kinase Inhibitor 2A), is a tumor suppressor gene located on human chromosome 9p21.3. It plays a crucial role in cell cycle regulation, specifically acting as a checkpoint at the G1 to S phase transition. This protein inhibits the activity of cyclin-dependent kinases 4 and 6 (CDK4 and CDK6). These kinases are essential for phosphorylating the retinoblastoma protein (pRb), a process that promotes cell proliferation. By inhibiting CDK4/6, p16INK4a prevents pRb phosphorylation, thus halting the cell cycle and preventing uncontrolled cell division.

The CDKN2A gene locus is complex and can produce multiple protein isoforms through alternative splicing and the use of different reading frames. Besides p16INK4a, it can also encode p14ARF, another tumor suppressor that stabilizes the p53 protein, further contributing to cell cycle control and apoptosis. Loss of function or reduced expression of p16INK4a is frequently observed in various cancers, including melanoma, glioblastoma, and non-small cell lung cancer. This loss allows cells to bypass the G1 checkpoint, leading to unchecked proliferation and tumor formation. Consequently, p16INK4a is considered a key player in cancer development and progression, and its inactivation is a common event in tumorigenesis. Research into p16INK4a's function continues to explore its potential as a therapeutic target.