Proliferative and Survival Effects of PUMA Promote Angiogenesis

The p53 upregulated modulator of apoptosis (PUMA) is known as an essential apoptosis inducer. Here, we report the seemingly paradoxical finding that PUMA is a proangiogenic factor critically required for the proliferation and survival of vascular and microglia cells. Strikingly, Puma deficiency by genetic deletion or small hairpin RNA knockdown inhibited developmental and pathological angiogenesis and reduced microglia numbers in vivo, whereas Puma gene delivery increased angiogenesis and cell survival. Mechanistically, we revealed that PUMA plays a critical role in regulating autophagy by modulating Erk activation and intracellular calcium level. Our findings revealed an unexpected function of PUMA in promoting angiogenesis and warrant more careful investigations into the therapeutic potential of PUMA in treating cancer and degenerative diseases. [Display omitted] ► PUMA is abundantly expressed in vascular and microglia cells ► PUMA promotes vascular/microglia cell proliferation/survival and angiogenesis ► Puma deficiency reduces angiogenesis and microglia density ► PUMA regulates autophagy, Erk activation, and intracellular calcium level Even though the p53 upregulated modulator of apoptosis (PUMA) gene has been known as an essential apoptosis inducer for many years, its effect on vascular and microglia cells is largely unknown. Now, Zhang and colleagues report their surprising finding that PUMA is a proangiogenic factor critically required for the proliferation and survival of vascular and microglia cells. Mechanistically, the authors reveal that PUMA plays a critical role in regulating autophagy by modulating Erk activation and intracellular calcium level.