FOXO3a-dependent regulation of Puma in response to cytokine/growth factor withdrawal.
Puma is an essential mediator of p53-dependent and -independent apoptosis in vivo. In response to genotoxic stress, Puma is induced in a p53-dependent manner. However, the transcription factor driving Puma up-regulation in response to p53-independent apoptotic stimuli has yet to be identified. Here, we show that FOXO3a up-regulates Puma expression in response to cytokine or growth factor deprivation. Importantly, dysregulated Akt signaling in lymphoid cells attenuated Puma induction upon cytokine withdrawal. Our results suggest that Puma, together with another BH3 only member, Bim, function as FOXO3a downstream targets to mediate a stress response when PI3K/Akt signaling is down-regulated.
You
Han
H
The Campbell family Institute for Breast Cancer Research, University Health Network, Toronto, Ontario M5G 2C1, Canada.
Pellegrini
Marc
M
Tsuchihara
Katsuya
K
Yamamoto
Kazuo
K
Hacker
Georg
G
Erlacher
Miriam
M
Villunger
Andreas
A
Mak
Tak W
TW
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D051017:Apoptosis Regulatory Proteins; D002460:Cell Line; D016207:Cytokines / Q000172:deficiency* / Q000235:genetics; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000502:physiology*; D005786:Gene Expression Regulation / Q000276:immunology; D006133:Growth Substances / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
D051017:Apoptosis Regulatory Proteins; D016207:Cytokines; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; C474033:FoxO3 protein, mouse; D006133:Growth Substances; C488588:PUMA protein, mouse; D025521:Tumor Suppressor Proteins