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Title 

Regulation of FOXO1 by TAK1-Nemo-like kinase pathway

 

TAK1-NLK 신호전달계에 의한 FOXO1의 조절

Authors 

Sunhong KimY S KimJ LeeJ Chung

Publisher 

American Society for Biochemistry and Molecular Biology

Issue Date 

2010

Citation 

Journal of Biological Chemistry, vol. 285, no. 11, pp. 8122-8129

Abstract 

The 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.

ISSN 

0021-9258

Link 

http://dx.doi.org/10.1074/jbc.M110.101824

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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