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Published on: January 7, 2019
FOXO3a-dependent regulation of Puma in response to cytokine/growth factor withdrawal
Han You1, Marc Pellegrini, Katsuya Tsuchihara
1The Campbell family Institute for Breast Cancer Research, University Health Network, Toronto, Ontario M5G 2C1, Canada.
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.
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