title: Proliferative and survival effects of PUMA promote angiogenesis.
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.
authors.affiliation: National Eye Institute, National Institutes of Health, Rockville, MD 20852, USA.
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.forename: Zhongshu
authors.initials: Z
authors.lastname: Tang
authors.forename: Anil
authors.initials: A
authors.lastname: Kumar
authors.forename: Chunsik
authors.initials: C
authors.lastname: Lee
authors.forename: Liping
authors.initials: L
authors.lastname: Zhang
authors.forename: Chaoyong
authors.initials: C
authors.lastname: Zhu
authors.forename: Anne
authors.initials: A
authors.lastname: Klotzsche-von Ameln
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.forename: Zhiqin
authors.initials: Z
authors.lastname: Gao
authors.forename: Shizhuang
authors.initials: S
authors.lastname: Zhang
authors.forename: Harald F
authors.initials: HF
authors.lastname: Langer
authors.forename: Xu
authors.initials: X
authors.lastname: Hou
authors.forename: Lasse
authors.initials: L
authors.lastname: Jensen
authors.forename: Wenxin
authors.initials: W
authors.lastname: Ma
authors.forename: Wai
authors.initials: W
authors.lastname: Wong
authors.forename: Triantafyllos
authors.initials: T
authors.lastname: Chavakis
authors.forename: Yizhi
authors.initials: Y
authors.lastname: Liu
authors.forename: Yihai
authors.initials: Y
authors.lastname: Cao
authors.forename: Xuri
authors.initials: X
authors.lastname: Li
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D001343:Autophagy; D002118:Calcium / Q000378:metabolism; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D002829:Choroid / Q000098:blood supply; D003315:Cornea / Q000098:blood supply; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D017628:Microglia / Q000166:cytology / Q000378:metabolism; D018919:Neovascularization, Physiologic; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D012160:Retina / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; C488588:PUMA protein, mouse; D034741:RNA, Small Interfering; D025521:Tumor Suppressor Proteins; D048049:Extracellular Signal-Regulated MAP Kinases; D002118:Calcium