ArticleGenes & development2003
Control of cell number by Drosophila FOXO: downstream and feedback regulation of the insulin receptor pathway.
Article in Genes & development, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 323 papers.
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Who cites it
323 citing papers in PubMed, 634 citations in OpenAlex.
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- Body-wide synchronization of insulin-signaling dependent DAF-16/FOXO nuclear translocation pulses correlated with C. elegans growth.Nature communications · 2025Article
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- The insulin-like peptides Dilp2 and Dilp6 exhibit divergent responses to dietary sugar and protein inProceedings of the National Academy of Sciences of the United States of America · 2025Article
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- The translational inhibitor 4EBP/Thor is required for Drosophila adaptation to hypoxia.Scientific reports · 2025Article
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263 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Drosophila insulin receptor (dInR) regulates cell growth and proliferation through the dPI3K/dAkt pathway, which is conserved in metazoan organisms. Here we report the identification and functional characterization of the Drosophila forkhead-related transcription factor dFOXO, a key component of the insulin signaling cascade. dFOXO is phosphorylated by dAkt upon insulin treatment, leading to cytoplasmic retention and inhibition of its transcriptional activity. Mutant dFOXO lacking dAkt phosphorylation sites no longer responds to insulin inhibition, remains in the nucleus, and is constitutively active. dFOXO activation in S2 cells induces growth arrest and activates two key players of the dInR/dPI3K/dAkt pathway: the translational regulator d4EBP and the dInR itself. Induction of d4EBP likely leads to growth inhibition by dFOXO, whereas activation of dInR provides a novel transcriptionally induced feedback control mechanism. Targeted expression of dFOXO in fly tissues regulates organ size by specifying cell number with no effect on cell size. Our results establish dFOXO as a key transcriptional regulator of the insulin pathway that modulates growth and proliferation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.