p16-INK4a Human, TAT

Cyclin-Dependent Kinase Inhibitor 2A (CDKN2A), also known as p16INK4a, is a crucial protein in the regulation of the cell cycle. It is encoded by the CDKN2A gene located on chromosome 9p21.3 in humans . This gene is known for its role in tumor suppression and is frequently mutated or deleted in various types of cancers .

The CDKN2A gene 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 amino acid sequences . The p16INK4a protein consists of four ankyrin repeats, each spanning 33 amino acid residues, forming a helix-turn-helix motif .

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 (Rb) protein, thereby blocking the transition from the G1 phase to the S phase of the cell cycle . The p14ARF protein, on the other hand, stabilizes the tumor suppressor protein p53 by interacting with and sequestering the E3 ubiquitin-protein ligase MDM2, which is responsible for p53 degradation .

Mutations and deletions in the CDKN2A gene are common in a wide variety of tumors, making it a significant tumor suppressor gene . Germline mutations in CDKN2A are associated with familial melanoma, glioblastoma, and pancreatic cancer . Additionally, the gene contains single nucleotide polymorphisms (SNPs) associated with an increased risk of coronary artery disease .

The human recombinant form of CDKN2A, often fused with the TAT peptide, is used in research to study its function and potential therapeutic applications. The TAT peptide facilitates the delivery of the recombinant protein into cells, allowing for the investigation of its effects on cell cycle regulation and tumor suppression.