Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor

Brunet A, Blenis J et al. · 1999 · Cell · Atlas ID BRU1999

What this study shows

Akt phosphorylates the Forkhead transcription factor FKHRL1 (a FOXO family member), driving its cytoplasmic retention via 14-3-3 binding and blocking Fas-ligand-driven apoptosis — the discovery that placed FOXO transcription factors downstream of Akt/PI3K survival signalling.

Abstract

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Survival factors can suppress apoptosis in a transcription-independent manner by activating the serine/threonine kinase Akt, which then phosphorylates and inactivates components of the apoptotic machinery, including BAD and Caspase 9. In this study, we demonstrate that Akt also regulates the activity of FKHRL1, a member of the Forkhead family of transcription factors. In the presence of survival factors, Akt phosphorylates FKHRL1, leading to FKHRL1's association with 14-3-3 proteins and FKHRL1's retention in the cytoplasm.

Read the full abstract on PubMed →

At a glance

Evidence type	M Molecular — cells, biochemistry, structure Marked M because it is molecular or in-vitro work (model: Mammalian cell lines; primary neurons (in vitro)) rather than a whole-organism health-outcome study. That is often exactly where causal biology gets established -- the code says which system the finding was shown in, and nothing about how good the work is.
Study type	5 - Mechanistic / In Vitro
Model system	Mammalian cell lines; primary neurons (in vitro)
Journal	Cell
Year	1999
Peer reviewed	Yes
Record last updated	2026-08-22
Source	DOI 10.1016/S0092-8674(00)80595-4 · PMID 10102273

Extracted findings

Intervention	Akt/PKB overexpression + survival-factor withdrawal (genetic)
Target	Akt / FOXO (FKHRL1)
Model	Mammalian cell lines; primary neurons (in vitro)
Effect	Akt phosphorylates FKHRL1 (FOXO), blocking its nuclear translocation and Fas-ligand-driven apoptosis upon survival-factor withdrawal

In the Atlas

Cite this paper

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Brunet, A., et al. (1999). Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell. https://doi.org/10.1016/S0092-8674(00)80595-4

@article{BRU1999,
  author       = {Brunet, A. and Blenis, J. and others},
  title        = {{Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor}},
  journal      = {Cell},
  year         = {1999},
  doi          = {10.1016/S0092-8674(00)80595-4},
  note         = {PMID: 10102273},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper.

Barton, O. (2026). Oliver's mTOR Atlas (record BRU1999) [Data set]. https://mtor-atlas.org/study/BRU1999/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_BRU1999,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record BRU1999},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/BRU1999/},
  doi          = {10.5281/zenodo.22059963}
}