PgmNr D1153: Kruppel homolog 1 represses dFOXO transcriptional activity and lipolysis.

Authors:
Hua Bai 1 ; Kang Ping 1 ; Kai Chang 1 ; Marc Tatar 2


Institutes
1) Iowa State University, Ames, IA; 2) Brown University, Providence, RI.


Keyword: insulin signaling

Abstract:

Insulin/insulin-like growth factor signaling (IIS) plays important roles in animal growth, metabolism, stress resistance and aging. It functions through the downstream forkhead transcription factor FOXO and interlays with many other key signaling pathways. The interaction between FOXO and its co-factors enhances the transcriptional specificity of insulin/FOXO signaling. Here, we identified transcriptional co-regulation of insulin signaling and lipolysis through the interaction between kruppel-like factor Kr-h1 and dFOXO in Drosophila. In fasting larvae, Kr-h1 co-localize with dFOXO in nuclei of fat body cells. Kr-h1 physically binds to dFOXO in vitro and acts as a repressor of dFOXO to regulate the transcriptional activation of insulin receptor (InR) and adipose TAG lipase brummer. The binding of Kr-h1 to the promoters of InR and brummer requires dFOXO. Juvenile hormone (JH) signaling, a major insect developmental regulator and an upstream regulator of Kr-h1, interacts with dFOXO to control lipolysis and the transcription of brummer lipase, and thus, lipolysis. Transcriptome analysis further reveals that Kr-h1 targets many metabolic genes that overlap with dFOXO targets. Thus, the interaction between Kr-h1 and dFOXO may represent a broad mechanism by which metabolic signaling integrates with JH-regulated developmental programs to coordinate organism growth.  .



Flybase Genetic Index:
1. FlyBase gene symbol: Kr-h1; FBgn: FBgn0266450
2. FlyBase gene symbol: foxo; FBgn: FBgn0038197
3. FlyBase gene symbol: InR; FBgn: FBgn0283499
4. FlyBase gene symbol: bmm; FBgn: FBgn0036449