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.
Funding Agencies|ERC (ENDHOMRET)||Deutsche Forschungsgemeinschaft|KFO 274|Volkswagen foundation (Lichtenberg program)||Swedish Research Council||Swedish Cancer Foundation||Karolinska Institute Foundation||Karolinska Institute Distinguished Professor Award||Tianjin Natural Science Foundation (CMM-Tianjin)|09ZCZDSF04400|Torsten Soderbergs Foundation||European Union Integrated Project of Metoxia|222741|European Research Council (ERC) ANGIOFAT|250021|Intramural Research Program of the NIH, National Eye Institute