Research Perspective Volume 1, Issue 9 pp 831—835

Figure 1. Schematic diagram summarizing the caveolin-1-dependent activation of the p53/p21 ^Waf1/Cip1/senescence pathway after oxidative stress. In resting cells, PP2A-C-dependent inhibition of ATM prevents the activation of p53. In addition, p53 is directly inhibited by binding to Mdm2. Oxidative stress promotes the sequestration of PP2A-C and Mdm2 by caveolin-1 leading to activation of p53 and its downstream target p21^Waf1/Cip1, and induction of premature senescence. Activation of the p53/p21^Waf1/Cip1/senescence pathway after oxidative stress is inhibited in cells lacking caveolin-1 expression. We suggest that activation of this pathway in lung fibroblasts by oxidants contained in cigarette smoke contributes to the development of pulmonary emphysema. Adapted from [33].