the drosophila foxa ortholog fork head regulates growth and gene expression downstream of target of rapamycin果蝇foxa直接同源叉头调节生长和下游基因表达的雷帕霉素的目标.pdf

The Drosophila FoxA Ortholog Fork Head Regulates Growth and Gene Expression Downstream of Target of Rapamycin ¨ 1,2,3 1,3,4 2 ¨ 1 Margret H. Bulow , Ruedi Aebersold , Michael J. Pankratz *, Martin A. Junger * 1 Institute of Molecular Systems Biology, Swiss Federal Institute of Technology (ETH) Zurich, Zurich, Switzerland, 2 Department of Molecular Brain Physiology and Behavior, Life and Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany, 3 Competence Center for Systems Physiology and Metabolic Diseases (CC- SPMD), Swiss Federal Institute of Technology (ETH) Zurich, Zurich, Switzerland, 4 Faculty of Science, University of Zurich, Zurich, Switzerland Abstract Forkhead transcription factors of the FoxO subfamily regulate gene expression programs downstream of the insulin signaling network. It is less clear which proteins mediate transcriptional control exerted by Target of rapamycin (TOR) signaling, but recent studies in nematodes suggest a role for FoxA transcription factors downstream of TOR. In this study we present evidence that outlines a similar connection in Drosophila, in which the FoxA protein Fork head (FKH) regulates cellular and organismal size downstream of TOR. We find that ectopic expression and targeted knockdown of FKH in larval tissues elicits different size phenotypes depending on nutrient state and TOR signaling levels. FKH overexpression has a negative effect on growth under fed conditions, and this phenotype is not further exacerbated by inhibition of TOR via rapamycin feeding. Under conditions of starvation or low TOR signaling levels, knockdown of FKH attenuates the size reductio