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Article: FOXO3a-dependent regulation of Pink1 (Park6) mediates survival signaling in response to cytokine deprivation

TitleFOXO3a-dependent regulation of Pink1 (Park6) mediates survival signaling in response to cytokine deprivation
Authors
KeywordsApoptosis
Transcription
Oxidative stress
Issue Date2009
Citation
Proceedings of the National Academy of Sciences of the United States of America, 2009, v. 106, n. 13, p. 5153-5158 How to Cite?
AbstractLoss-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 antioxidative stress factors.
Persistent Identifierhttp://hdl.handle.net/10722/291889
ISSN
2020 Impact Factor: 11.205
2020 SCImago Journal Rankings: 5.011
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorMei, Yang-
dc.contributor.authorZhang, Yiru-
dc.contributor.authorYamamoto, Kazuo-
dc.contributor.authorXie, Wei-
dc.contributor.authorMak, Tak W.-
dc.contributor.authorYou, Han-
dc.date.accessioned2020-11-17T14:55:19Z-
dc.date.available2020-11-17T14:55:19Z-
dc.date.issued2009-
dc.identifier.citationProceedings of the National Academy of Sciences of the United States of America, 2009, v. 106, n. 13, p. 5153-5158-
dc.identifier.issn0027-8424-
dc.identifier.urihttp://hdl.handle.net/10722/291889-
dc.description.abstractLoss-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 antioxidative stress factors.-
dc.languageeng-
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of America-
dc.subjectApoptosis-
dc.subjectTranscription-
dc.subjectOxidative stress-
dc.titleFOXO3a-dependent regulation of Pink1 (Park6) mediates survival signaling in response to cytokine deprivation-
dc.typeArticle-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1073/pnas.0901104106-
dc.identifier.pmid19276113-
dc.identifier.pmcidPMC2654023-
dc.identifier.scopuseid_2-s2.0-65249108225-
dc.identifier.volume106-
dc.identifier.issue13-
dc.identifier.spage5153-
dc.identifier.epage5158-
dc.identifier.eissn1091-6490-
dc.identifier.isiWOS:000264790600037-
dc.identifier.issnl0027-8424-

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