Figure 2: Cyclin dependant kinases are responsive to mutiple signals. The genotoxic stresses such as DNA damage leads to the induction of p21cip1 through upregulation of p53. TGF-β mediated growth-inhibitory responses act on both p15INK4B or p27KIP1. Cyclin activating kinase (CAK) and phosphatses (CDC25) regulates CDKs via phosphorylation and dephosphorylation respectively. Growth factors and RAS signal CDKs through cyclin D and transcription factors (E2F) through cyclin E. p16INK4A gets upregulated due to cellular ageing or senescence.