Fig. 7. A signaling model for TSP1-induced senescence.
Upon binding to CD47, TSP1 activates the Nox1 complex, which generates robust and sustained accumulation of ROS. In turn, this triggers committed senescence through a pathway involving p53-p21cip–induced DNA damage response and decreased Rb phosphorylation. This pathway can be disrupted using the selective Nox1 inhibitor NoxA1ds.