TRB1 negatively regulates gluconeogenesis by suppressing the transcriptional activity of FOXO1

被引：5

作者：

Tsuzuki, Kaori ^{[1
]}

Itoh, Yuka ^{[1
,2
]}

Inoue, Yasumichi ^{[1
,3
]}

Hayashi, Hidetoshi ^{[1
,3
]}

机构：

[1] Nagoya City Univ, Dept Cell Signaling, Grad Sch Pharmaceut Sci, Nagoya, Aichi 4678603, Japan

[2] Univ Yamanashi, Dept Biochem, Grad Sch Med, Yamanashi, Japan

[3] Nagoya City Univ, Dept Innovat Therapeut Sci, Cooperat Major Nanopharmaceut Sci, Grad Sch Pharmaceut Sci, Nagoya, Aichi, Japan

来源：

FEBS LETTERS | 2019年 / 593卷 / 03期

基金：

日本学术振兴会;

关键词：

acetylation; CBP; FOXO1; glucose metabolism; TRB1; TRIBBLES HOMOLOG; CELL-SURVIVAL; PROTEIN; GENE; INSULIN; TRIB1; PHOSPHORYLATION; MORPHOGENESIS; PSEUDOKINASE; ACETYLATION;

D O I：

10.1002/1873-3468.13314

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Tribbles related homolog 1 is the mammalian ortholog of Tribbles, which controls cell division and migration during development in Drosophila. TRB1 is a pseudokinase and functions as a scaffold protein. Recent findings suggest that TRB1 plays important roles in hepatic lipid metabolism and participates in insulin resistance. However, the underlying mechanisms have not yet been elucidated. Here, we demonstrate that TRB1 suppresses FOXO1 transcriptional activity to downregulate the expression of G6Pase and PEPCK, which encode gluconeogenic rate-limiting enzymes. TRB1 knockdown enhances FOXO1 binding to the gluconeogenic gene promoters. It also increases FOXO1 acetylation and recruits CBP to the binding sequence of FOXO1. These results suggest that TRB1 suppresses the expression of G6Pase and PEPCK by attenuating FOXO1 transcriptional activity and negatively regulates gluconeogenesis.

引用

页码：369 / 380

页数：12

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