Dynamic FoxO transcription factors

Haojie Huang, Donald J. Tindall

Research output: Contribution to journalArticle

685 Citations (Scopus)

Abstract

Forkhead box O (FoxO) transcription factors FoxOl, FoxO3a, FoxO4 and FoxO6, the mammalian orthologs of Caenorhabditis elegans DAF-16, are emerging as an important family of proteins that modulate the expression of genes involved in apoptosis, the cell cycle, DNA damage repair, oxidative stress, cell differentiation, glucose metabolism and other cellular functions. FoxO proteins are regulated by multiple mechanisms. They undergo inhibitory phosphorylation by protein kinases such as Akt, SGK, IKK and CDK2 in response to external and internal stimuli. By contrast, they are activated by upstream regulators such as JNK and MST1 under stress conditions. Their activities are counterbalanced by the acetylases CBP and p300 and the deacetylase SIRT1. Also, whereas polyubiquitylation of FoxO1 and FoxO3a leads to their degradation by the proteasome, monoubiquitylation of FoxO4 facilitates its nuclear localization and augments its transcriptional activity. Thus, the potent functions of FoxO proteins are tightly controlled by complex signaling pathways under physiological conditions; dysregulation of these proteins may ultimately lead to disease such as cancer.

Original languageEnglish (US)
Pages (from-to)2479-2487
Number of pages9
JournalJournal of Cell Science
Volume120
Issue number15
DOIs
StatePublished - Aug 1 2007

Fingerprint

Forkhead Transcription Factors
Acetylesterase
Caenorhabditis elegans
Proteasome Endopeptidase Complex
DNA Repair
Protein Kinases
DNA Damage
Cell Differentiation
Cell Cycle
Proteins
Oxidative Stress
Phosphorylation
Apoptosis
Gene Expression
Glucose
Neoplasms

Keywords

  • Akt
  • Cancer
  • CDK2
  • FoxO
  • Phosphorylation
  • Ubiquitylation

ASJC Scopus subject areas

  • Cell Biology

Cite this

Dynamic FoxO transcription factors. / Huang, Haojie; Tindall, Donald J.

In: Journal of Cell Science, Vol. 120, No. 15, 01.08.2007, p. 2479-2487.

Research output: Contribution to journalArticle

Huang, Haojie ; Tindall, Donald J. / Dynamic FoxO transcription factors. In: Journal of Cell Science. 2007 ; Vol. 120, No. 15. pp. 2479-2487.
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