INK4

INK4 refers to a family of tumor suppressor proteins that play a critical role in regulating the cell cycle. This family includes four main members: p16INK4a (CDKN2A), p15INK4b (CDKN2B), p18INK4c (CDKN2C), and p19INK4d (CDKN2D). The most extensively studied member is p16INK4a, which is encoded by the CDKN2A gene.

These proteins function by inhibiting cyclin-dependent kinases (CDKs) 4 and 6. CDKs 4 and 6, when activated by their cyclin partners (cyclin D), phosphorylate the retinoblastoma protein (Rb). Phosphorylation of Rb releases transcription factors like E2F, which are necessary for the progression of the cell cycle from the G1 phase to the S phase. By binding to and inhibiting CDKs 4 and 6, INK4 proteins prevent Rb phosphorylation and thus block cell cycle progression. This mechanism is crucial for maintaining cellular quiescence and preventing uncontrolled proliferation.

Mutations or deletions in the genes encoding INK4 proteins, particularly CDKN2A, are frequently observed in various cancers, including melanoma, glioblastoma, and pancreatic cancer. Loss of INK4 function leads to aberrant cell cycle progression and contributes to tumor development and progression. Therefore, INK4 proteins are considered key gatekeepers of the cell cycle. Their regulatory role makes them important targets for cancer research and potential therapeutic strategies.