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	FOXO3a-dependent regulation of Pink1 (Park6) mediates survival signaling in response to cytokine deprivation
	Mei, Yang ; Mei Y(梅杨) ; Zhang, Yiru ; Zhang YR(张毅汝) ; Yamamoto, Kazuo（ Princess Margaret Hosp, Campbell Family Inst Breast Canc Res, Toronto） ; Xie, Wei ; Mak, Tak W.（ Princess Margaret Hosp, Campbell Family Inst Breast Canc Res, Toronto） ; You, Han ; You H(尤涵)
	2009
关键词	apoptosis oxidative stress transcription
英文摘要	Loss-of-function mutations of phosphatase/tensin homolog deleted on chromosome 10 (PTEN)-induced putative kinase 1 (Pink1) (also known as Park6) identified in familial forms of Parkinson's disease (PD) are associated with compromised mitochondrial function. Emerging data suggest that Pink1 is an essential pro-survival factor that is induced in response to oxidative stress. However, the mechanisms regulating Pink1 expression under stress conditions remain unknown. Forkhead box, subgroup O (FOXO) transcription factors carry out distinct biological functions in response to different extracellular signals. Notably, FOXO factors possess evolutionarily conserved roles in protecting cells from oxidative stress-induced death. Here we report that the FOXO family member FOXO3a controls Pink1 transcription in both mouse and human cells subjected to growth factor deprivation and that this regulation is exerted through evolutionarily conserved FOXO binding elements. Induction of Pink1 by FOXO3a is crucial for survival signals in lymphocytes, as depletion of Pink1 sensitizes these cells to death induced by deprivation of an essential growth factor. Our data reveal that the role of FOXO factors in protecting cells from growth factor deprivation-triggered apoptosis has been underestimated and that FOXOs mediate this protection by transactivating anti-apoptotic effectors like Pink1. Given the essential role of Pink1 in combating cell death, our findings may help to dissect the mechanisms by which FOXO proteins function as anti-oxidative stress factors.; National Natural Science Foundation of China [30700130]; Ministry of Science and Technology of China [2009CB522200]
语种	英语
出版者	NATL ACAD SCIENCES
内容类型	期刊论文
源URL	[http://dx.doi.org/doi:10.1073/pnas.0901104106]
专题	生命科学－已发表论文
推荐引用方式 GB/T 7714	Mei, Yang,Mei Y,Zhang, Yiru,et al. FOXO3a-dependent regulation of Pink1 (Park6) mediates survival signaling in response to cytokine deprivation[J],2009.
APA	Mei, Yang.,梅杨.,Zhang, Yiru.,张毅汝.,Yamamoto, Kazuo.,...&尤涵.(2009).FOXO3a-dependent regulation of Pink1 (Park6) mediates survival signaling in response to cytokine deprivation..
MLA	Mei, Yang,et al."FOXO3a-dependent regulation of Pink1 (Park6) mediates survival signaling in response to cytokine deprivation".(2009).

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