4E-BP functions as a metabolic brake used under stress conditions but not during normal growth.
4E-BP is an important regulator of overall translation levels in cells. By binding eIF4E, 4E-BP impairs recruitment of the 40S ribosomal subunit to the cap structure present at the 5'-end of all eukaryotic cellular mRNAs. 4E-BP activity is controlled by TOR (Target of Rapamycin). 4E-BP has been studied extensively in cell culture; however, the biological role of 4E-BP in developing organisms is unclear to date. Since TOR has been shown to control tissue growth during animal development, 4E-BP has also been assumed to serve as a growth regulator. Here, we study the relevance of 4E-BP function for organismal development, and present evidence for an alternate view. We show that 4E-BP strongly affects fat metabolism in Drosophila. We suggest that 4E-BP works as a metabolic brake that is activated under conditions of environmental stress to control fat metabolism. 4E-BP mutants lack this regulation, reducing their ability to survive under unfavorable conditions.
Teleman
Aurelio A
AA
European Molecular Biology Laboratory, Heidelberg, Germany.
Chen
Ya-Wen
YW
Cohen
Stephen M
SM
D000818:Animals; D049628:Body Size / Q000235:genetics / Q000502:physiology*; D029721:Drosophila Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D004331:Drosophila melanogaster / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism*; D007113:Immunity, Innate / Q000502:physiology; D008136:Longevity / Q000235:genetics; D009154:Mutation; D013312:Stress, Physiological / Q000378:metabolism*
D029721:Drosophila Proteins; D039561:Eukaryotic Initiation Factor-4E; C105238:cup protein, Drosophila