Research Paper Volume 15, Issue 10 pp 4012—4034

Key elements of cellular senescence involve transcriptional repression of mitotic and DNA repair genes through the p53-p16/RB-E2F-DREAM complex


Figure 6. Mechanisms proposed in this study. p53/p21-p16/RB-E2F-DREAM repressor complex controls senescence. p16INK4A and p53 are two master regulators of cellular senescence. Cell stress or DNA damage signals lead to activation p53 and transcriptional upregulation of the CDK inhibitor p21/CDKN1A, which in-turn hypophosphorylates RB. Activation of p16 INK4A controls phosphorylation of RB by binding to CDK4/6 and inhibiting the action of cyclin D. The active form of RB interacts with E2F to restrict transcription of genes that control cell cycle transition. RB-E2F and DREAM complex appear to cooperate to repress many genes that are required for G1/2 to G2/M transitions, potentially leading to impaired proliferation, defective DNA damage repair, altered chromatin, and establishment of senescence. (Created with