title: FOXO3a-dependent regulation of Puma in response to cytokine/growth factor withdrawal.
abstract: 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.
authors.affiliation: The Campbell family Institute for Breast Cancer Research, University Health Network, Toronto, Ontario M5G 2C1, Canada.
authors.forename: Han
authors.initials: H
authors.lastname: You
authors.forename: Marc
authors.initials: M
authors.lastname: Pellegrini
authors.forename: Katsuya
authors.initials: K
authors.lastname: Tsuchihara
authors.forename: Kazuo
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Georg
authors.initials: G
authors.lastname: Hacker
authors.forename: Miriam
authors.initials: M
authors.lastname: Erlacher
authors.forename: Andreas
authors.initials: A
authors.lastname: Villunger
authors.forename: Tak W
authors.initials: TW
authors.lastname: Mak
mesh_terms: 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*
chemical_list: 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