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FOXO4 is acetylated upon peroxide stress and deacetylated by the longevity protein hSir2(SIRT1).
J Biol Chem. 2004 Jul 09; 279(28):28873-9.JB

Abstract

FOXO transcription factors have important roles in metabolism, cellular proliferation, stress tolerance, and aging. FOXOs are negatively regulated by protein kinase B/c-Akt-mediated phosphorylation. Here we show that FOXO factors are also subject to regulation by reversible acetylation. We provide evidence that the acetyltransferase CREB-binding protein (CBP) binds FOXO resulting in acetylation of FOXO. This acetylation inhibits FOXO transcriptional activity. Binding of CBP and acetylation are induced after treatment of cells with peroxide stress. Deacetylation of FOXOs involves binding of the NAD-dependent deacetylase hSir2(SIRT1). Accordingly, hSir2(SIRT1)-mediated deacetylation precludes FOXO inhibition through acetylation and thereby prolongs FOXO-dependent transcription of stress-regulating genes. These data demonstrate that acetylation functions in a second pathway of negative control for FOXO factors and provides a novel mechanism whereby hSir2(SIRT1) can promote cellular survival and increase lifespan.

Authors+Show Affiliations

Department of Physiological Chemistry, Center for Biomedical Genetics, University Medical Center Utrecht, 3584 CG Utrecht, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15126506

Citation

van der Horst, Armando, et al. "FOXO4 Is Acetylated Upon Peroxide Stress and Deacetylated By the Longevity Protein HSir2(SIRT1)." The Journal of Biological Chemistry, vol. 279, no. 28, 2004, pp. 28873-9.
van der Horst A, Tertoolen LG, de Vries-Smits LM, et al. FOXO4 is acetylated upon peroxide stress and deacetylated by the longevity protein hSir2(SIRT1). J Biol Chem. 2004;279(28):28873-9.
van der Horst, A., Tertoolen, L. G., de Vries-Smits, L. M., Frye, R. A., Medema, R. H., & Burgering, B. M. (2004). FOXO4 is acetylated upon peroxide stress and deacetylated by the longevity protein hSir2(SIRT1). The Journal of Biological Chemistry, 279(28), 28873-9.
van der Horst A, et al. FOXO4 Is Acetylated Upon Peroxide Stress and Deacetylated By the Longevity Protein HSir2(SIRT1). J Biol Chem. 2004 Jul 9;279(28):28873-9. PubMed PMID: 15126506.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - FOXO4 is acetylated upon peroxide stress and deacetylated by the longevity protein hSir2(SIRT1). AU - van der Horst,Armando, AU - Tertoolen,Leon G J, AU - de Vries-Smits,Lydia M M, AU - Frye,Roy A, AU - Medema,René H, AU - Burgering,Boudewijn M T, Y1 - 2004/05/04/ PY - 2004/5/6/pubmed PY - 2004/8/25/medline PY - 2004/5/6/entrez SP - 28873 EP - 9 JF - The Journal of biological chemistry JO - J. Biol. Chem. VL - 279 IS - 28 N2 - FOXO transcription factors have important roles in metabolism, cellular proliferation, stress tolerance, and aging. FOXOs are negatively regulated by protein kinase B/c-Akt-mediated phosphorylation. Here we show that FOXO factors are also subject to regulation by reversible acetylation. We provide evidence that the acetyltransferase CREB-binding protein (CBP) binds FOXO resulting in acetylation of FOXO. This acetylation inhibits FOXO transcriptional activity. Binding of CBP and acetylation are induced after treatment of cells with peroxide stress. Deacetylation of FOXOs involves binding of the NAD-dependent deacetylase hSir2(SIRT1). Accordingly, hSir2(SIRT1)-mediated deacetylation precludes FOXO inhibition through acetylation and thereby prolongs FOXO-dependent transcription of stress-regulating genes. These data demonstrate that acetylation functions in a second pathway of negative control for FOXO factors and provides a novel mechanism whereby hSir2(SIRT1) can promote cellular survival and increase lifespan. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/15126506/FOXO4_is_acetylated_upon_peroxide_stress_and_deacetylated_by_the_longevity_protein_hSir2_SIRT1__ L2 - http://www.jbc.org/cgi/pmidlookup?view=long&pmid=15126506 DB - PRIME DP - Unbound Medicine ER -