Regulation of FOXO1 by TAK1-Nemo-like kinase pathway = TAK1-NLK 신호전달계에 의한 FOXO1의 조절

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dc.contributor.authorSunhong Kim-
dc.contributor.authorY S Kim-
dc.contributor.authorJ Lee-
dc.contributor.authorJ Chung-
dc.description.abstractThe FOXO family of forkhead transcription factors has a variety of important functions in stress response, metabolism, cell cycle, apoptosis, longevity, etc. The transcriptional activity and subcellular localization of FOXO are tightly regulated by post-translational modifications, including phosphorylation by various kinases. Here, we report that the transforming growth factor-beta-activated kinase (TAK1)-Nemo-like kinase (NLK) pathway negatively regulates FOXO1. We show that NLK binds and phosphorylates FOXO1 at Pro-directed Ser/Thr residues in the transactivation domain. The phosphorylation by TAK1-NLK pathway inhibits the transcriptional activity of FOXO1 and excludes FOXO1 from the nucleus, which is independent of phosphatidylinositol 3-kinase/Akt pathway. Consistently, knockdown of TAK1-NLK pathway dephosphorylates FOXO1 and decreases phospho-Ser-329 FOXO1 level. It also induces translocation of FOXO1 into the nucleus and leads to an increase in mRNA levels of FOXO target genes and poly(ADP-ribose) polymerase cleavage. In addition, we show the interaction between NLK and FOXO1 is evolutionarily conserved in Drosophila. Collectively, these findings provide the first evidence that TAK1-NLK pathway is a novel regulator of FOXO1.-
dc.publisherAmer Soc Biochemistry Molecular Biology Inc-
dc.titleRegulation of FOXO1 by TAK1-Nemo-like kinase pathway = TAK1-NLK 신호전달계에 의한 FOXO1의 조절-
dc.title.alternativeRegulation of FOXO1 by TAK1-Nemo-like kinase pathway-
dc.citation.titleJournal of Biological Chemistry-
dc.contributor.affiliatedAuthorSunhong Kim-
dc.identifier.bibliographicCitationJournal of Biological Chemistry, vol. 285, no. 11, pp. 8122-8129-
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