REPTOR and REPTOR-BP regulate organismal metabolism and transcription downstream of TORC1

TORC1 regulates growth and metabolism in part by influencing transcriptional programs. We identify here REPTOR and REPTOR-BP as transcription factors downstream of TORC1, required for ∼90% of the transcriptional induction that occurs upon TORC1 inhibition in Drosophila. Thus REPTOR and REPTOR-BP are...

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Bibliographic Details
Published in:Developmental cell 2015-05, Vol.33 (3), p.272-284
Main Authors: Tiebe, Marcel, Lutz, Marilena, De La Garza, Adriana, Buechling, Tina, Boutros, Michael, Teleman, Aurelio A.
Format: Article
Language:English
Subjects:
Animals
CREBL2
CREBRF
development
Drosophila
Drosophila melanogaster - metabolism
Drosophila Proteins - metabolism
Gene Knockdown Techniques
Homeostasis - physiology
Mechanistic Target of Rapamycin Complex 1
metabolism
Multiprotein Complexes - metabolism
Phosphorylation - physiology
Signal Transduction - physiology
starvation
TOR Serine-Threonine Kinases - metabolism
Transcription Factors - metabolism
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Summary:TORC1 regulates growth and metabolism in part by influencing transcriptional programs. We identify here REPTOR and REPTOR-BP as transcription factors downstream of TORC1, required for ∼90% of the transcriptional induction that occurs upon TORC1 inhibition in Drosophila. Thus REPTOR and REPTOR-BP are major effectors of the transcriptional stress response induced upon TORC1 inhibition, analogous to the role of FOXO downstream of Akt. We find that when TORC1 is active, it phosphorylates REPTOR on Ser527 and Ser530, leading to REPTOR cytoplasmic retention. Upon TORC1 inhibition, REPTOR becomes dephosphorylated in a PP2A dependent manner, shuttles into the nucleus, joins its partner REPTOR-BP to bind target genes, and activates their transcription. In vivo functional analysis using knockout flies reveals that REPTOR and REPTOR-BP play critical roles in maintaining energy homeostasis and promoting animal survival upon nutrient restriction.
ISSN:1534-5807
1878-1551
DOI:10.1016/j.devcel.2015.03.013