COVID-19 Response: Local Logistics     National Effort

ROS Inhibits Cell Growth by Regulating 4EBP and S6K, Independent of TOR, during Development [Transgenic Fly Facility].

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TitleROS Inhibits Cell Growth by Regulating 4EBP and S6K, Independent of TOR, during Development [Transgenic Fly Facility].
Publication TypeJournal Article
Year of Publication2019
AuthorsToshniwal AG, Gupta S, Mandal L, Mandal S
JournalDev Cell
Volume49
Issue3
Pagination473-489.e9
Date Published2019 May 06
ISSN1878-1551
Abstract

Reactive oxygen species (ROS), despite having damaging roles, serve as signaling molecules regulating diverse biological and physiological processes. Employing in vivo genetic studies in Drosophila, we show that besides causing G1-S arrest by activation of Dacapo, ROS can simultaneously inhibit cell growth by regulating the expression of 4EBP and S6K. This is achieved by triggering a signaling cascade that includes Ask1, JNK, and FOXO independent of the Tsc-TOR growth regulatory pathway. Qualitative and quantitative differences in the types of ROS molecules generated dictate whether cells undergo G1-S arrest only or experience blocks in both cell proliferation and growth. Importantly, during normal development, this signaling cascade is triggered by ecdysone in late larval fat body cells to restrict their growth prior to pupation by antagonizing insulin signaling. The present work reveals an unexpected role of ROS in systemic control of growth in response to steroid hormone signaling to establish organismal size.

DOI10.1016/j.devcel.2019.04.008
Alternate JournalDev. Cell
PubMed ID31063760