Abstract
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.
Copyright © 2012 The Authors. Published by Elsevier Inc. All rights reserved.
Publication types
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Research Support, N.I.H., Intramural
MeSH terms
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Animals
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Aorta / metabolism
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Apoptosis Regulatory Proteins / antagonists & inhibitors
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Apoptosis Regulatory Proteins / genetics
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Apoptosis Regulatory Proteins / metabolism*
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Autophagy
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Calcium / metabolism
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Cell Proliferation
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Cell Survival
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Cells, Cultured
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Choroid / blood supply
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Cornea / blood supply
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Endothelial Cells / cytology
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Endothelial Cells / metabolism
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Extracellular Signal-Regulated MAP Kinases / metabolism
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Human Umbilical Vein Endothelial Cells
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Humans
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Mice
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Mice, Knockout
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Microglia / cytology
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Microglia / metabolism
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Neovascularization, Physiologic*
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RNA Interference
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RNA, Small Interfering / metabolism
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Retina / metabolism
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Tumor Suppressor Proteins / antagonists & inhibitors
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Tumor Suppressor Proteins / genetics
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Tumor Suppressor Proteins / metabolism*
Substances
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Apoptosis Regulatory Proteins
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PUMA protein, mouse
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RNA, Small Interfering
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Tumor Suppressor Proteins
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Extracellular Signal-Regulated MAP Kinases
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Calcium