p16-INK4a Human

The CDKN2A gene is quite unique as it encodes two distinct proteins through alternative splicing: p16INK4a and p14ARF. These proteins are transcribed from the same second and third exons but have different first exons, resulting in different reading frames and thus different amino acid sequences .

• p16INK4a: This protein belongs to the INK4 family and consists of four ankyrin repeats, each forming a helix-turn-helix motif. These motifs are connected by loops, creating a structure that is essential for its function as a cyclin-dependent kinase inhibitor .
• p14ARF: Known as p19ARF in mice, this protein plays a role in stabilizing the tumor suppressor protein p53 by interacting with and sequestering MDM2, a protein responsible for p53 degradation .

CDKN2A plays a pivotal role in cell cycle regulation by inhibiting cyclin-dependent kinases 4 and 6 (CDK4 and CDK6). This inhibition prevents the phosphorylation of the retinoblastoma protein (Rb), thereby blocking the transition from the G1 phase to the S phase of the cell cycle . This mechanism is crucial for controlling cell proliferation and preventing uncontrolled cell growth, which can lead to tumor formation.

• p16INK4a: Inhibits CDK4 and CDK6, leading to the activation of the Rb protein, which in turn blocks cell cycle progression .
• p14ARF: Activates the p53 tumor suppressor pathway by sequestering MDM2, thus preventing the degradation of p53 and promoting cell cycle arrest and apoptosis .

Mutations and deletions in the CDKN2A gene are commonly associated with various types of cancers. It is considered one of the most frequently inactivated tumor suppressor genes, second only to p53 . Germline mutations in CDKN2A are linked to familial melanoma, glioblastoma, and pancreatic cancer . Additionally, CDKN2A is involved in other diseases, such as coronary artery disease, due to its role in cell cycle regulation and tumor suppression .

Recombinant CDKN2A (Human) is produced using recombinant DNA technology, which allows for the expression of the human CDKN2A gene in a host organism, typically bacteria or yeast. This recombinant protein is used in research to study its function, interactions, and potential therapeutic applications. It is particularly valuable in cancer research, where understanding the mechanisms of CDKN2A can lead to the development of targeted therapies and diagnostic tools.