Suppression of FOXO1 activity by FHL2 through SIRT1-mediated deacetylation
Open Access
- 3 February 2005
- journal article
- Published by Springer Nature in The EMBO Journal
- Vol. 24 (5) , 1021-1032
- https://doi.org/10.1038/sj.emboj.7600570
Abstract
Forkhead box class O (FOXO) proteins are transcription factors that function downstream of the PTEN tumor suppressor and directly control the expression of genes involved in apoptosis, cell cycle progression, and stress responses. In the present study, we show that FOXO1 interacts with four and a half LIM 2 (FHL2) in prostate cancer cells. This interaction occurred in the nucleus and was enhanced by lysophosphatic acid. FHL2 decreased the transcriptional activity of FOXO1 and the expression of known FOXO target genes and inhibited FOXO1‐induced apoptosis. Interestingly, SIRT1, a mammalian homolog of yeast Sir2, bound to and deacetylated FOXO1 and inhibited its transcriptional activity. FHL2 enhanced the interaction of FOXO1 and SIRT1 and the deacetylation of FOXO1 by Sirtuin‐1 (SIRT1). Overall, our data show that FHL2 inhibits FOXO1 activity in prostate cancer cells by promoting the deacetylation of FOXO1 by SIRT1.Keywords
This publication has 50 references indexed in Scilit:
- IκB Kinase Promotes Tumorigenesis through Inhibition of Forkhead FOXO3aPublished by Elsevier ,2004
- Stress-Dependent Regulation of FOXO Transcription Factors by the SIRT1 DeacetylaseScience, 2004
- Extracellular Signal-Regulated Kinase 2 Interacts with and Is Negatively Regulated by the LIM-Only Protein FHL2 in CardiomyocytesMolecular and Cellular Biology, 2004
- Identification of the LIM Protein FHL2 as a Coactivator of β-CateninJournal of Biological Chemistry, 2003
- Regulation of Estrogen Receptor Nuclear Export by Ligand-Induced and p38-Mediated Receptor PhosphorylationMolecular and Cellular Biology, 2002
- Ligand-dependent Interaction of Estrogen Receptor-α with Members of the Forkhead Transcription Factor FamilyPublished by Elsevier ,2001
- Molecular interaction of dihydropyridine receptors with type-1 ryanodine receptors in rat brainBiochemical Journal, 2001
- MEKK1 Activation of Human Estrogen Receptor and Stimulation of the Agonistic Activity of 4-Hydroxytamoxifen in Endometrial and Ovarian Cancer CellsMolecular Endocrinology, 2000
- A C. elegans mutant that lives twice as long as wild typeNature, 1993
- Fusion of a fork head domain gene to PAX3 in the solid tumour alveolar rhabdomyosarcomaNature Genetics, 1993