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REPTOR and REPTOR-BP Regulate Organismal Metabolism and Transcription Downstream of TORC1.

Abstract：

:TORC1 regulates growth and metabolism, in part, by influencing transcriptional programs. Here, we identify REPTOR and REPTOR-BP as transcription factors downstream of TORC1 that are 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.

journal_name

Dev Cell

journal_title

Developmental cell

authors

Tiebe M,Lutz M,De La Garza A,Buechling T,Boutros M,Teleman AA

doi

10.1016/j.devcel.2015.03.013

subject

Has Abstract

pub_date

2015-05-04 00:00:00

pages

272-84

issue

3

eissn

1534-5807

issn

1878-1551

pii

S1534-5807(15)00181-1

journal_volume

33

pub_type

杂志文章

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