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Suppression of FOXO1 activity by FHL2 through SIRT1-mediated deacetylation.
EMBO J. 2005 Mar 09; 24(5):1021-32.EJ

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.

Authors+Show Affiliations

Department of Pathology, University of South Florida College of Medicine, Drug Discovery and Experimental Therapeutics, H Lee Moffitt Cancer Center, Tampa, FL 33612, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15692560

Citation

Yang, Yonghua, et al. "Suppression of FOXO1 Activity By FHL2 Through SIRT1-mediated Deacetylation." The EMBO Journal, vol. 24, no. 5, 2005, pp. 1021-32.
Yang Y, Hou H, Haller EM, et al. Suppression of FOXO1 activity by FHL2 through SIRT1-mediated deacetylation. EMBO J. 2005;24(5):1021-32.
Yang, Y., Hou, H., Haller, E. M., Nicosia, S. V., & Bai, W. (2005). Suppression of FOXO1 activity by FHL2 through SIRT1-mediated deacetylation. The EMBO Journal, 24(5), 1021-32.
Yang Y, et al. Suppression of FOXO1 Activity By FHL2 Through SIRT1-mediated Deacetylation. EMBO J. 2005 Mar 9;24(5):1021-32. PubMed PMID: 15692560.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Suppression of FOXO1 activity by FHL2 through SIRT1-mediated deacetylation. AU - Yang,Yonghua, AU - Hou,Huayan, AU - Haller,Edward M, AU - Nicosia,Santo V, AU - Bai,Wenlong, Y1 - 2005/02/03/ PY - 2004/09/06/received PY - 2005/01/07/accepted PY - 2005/2/5/pubmed PY - 2005/4/29/medline PY - 2005/2/5/entrez SP - 1021 EP - 32 JF - The EMBO journal JO - EMBO J. VL - 24 IS - 5 N2 - 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. SN - 0261-4189 UR - https://www.unboundmedicine.com/medline/citation/15692560/Suppression_of_FOXO1_activity_by_FHL2_through_SIRT1_mediated_deacetylation_ L2 - https://doi.org/10.1038/sj.emboj.7600570 DB - PRIME DP - Unbound Medicine ER -