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Updated: Aug 11, 2026

Deacetylation Assays to Unravel the Interplay between Sirtuins (SIRT2) and Specific Protein-substrates
14:32

Deacetylation Assays to Unravel the Interplay between Sirtuins (SIRT2) and Specific Protein-substrates

Published on: February 27, 2016

Suppression of FOXO1 activity by FHL2 through SIRT1-mediated deacetylation

Yonghua Yang1, Huayan Hou, Edward M Haller

  • 1Department of Pathology, University of South Florida College of Medicine, Drug Discovery and Experimental Therapeutics, H Lee Moffitt Cancer Center, Tampa, FL 33612, USA.

The EMBO Journal
|February 5, 2005
PubMed

Insights

In prostate cancer, four and a half LIM 2 (FHL2) protein interacts with Forkhead box class O (FOXO1). FHL2 promotes SIRT1-mediated deacetylation of FOXO1, inhibiting its activity and promoting cancer cell survival.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Cellular Signaling

Background:

  • Forkhead box class O (FOXO) proteins are key transcription factors regulating apoptosis, cell cycle, and stress responses.
  • FOXO proteins act downstream of the PTEN tumor suppressor pathway, crucial in cancer development.

Purpose of the Study:

  • To investigate the interaction between FOXO1 and four and a half LIM 2 (FHL2) in prostate cancer cells.
  • To elucidate the mechanism by which FHL2 affects FOXO1 transcriptional activity and function.

Main Methods:

  • Co-immunoprecipitation to detect protein-protein interactions.
  • Reporter assays to measure transcriptional activity.
  • Western blotting to assess protein levels and modifications (deacetylation).

Main Results:

  • FOXO1 interacts with FHL2 in the nucleus of prostate cancer cells, an interaction enhanced by lysophosphatidic acid.
  • FHL2 significantly decreases FOXO1 transcriptional activity and the expression of FOXO target genes, thereby inhibiting FOXO1-induced apoptosis.
  • Sirtuin-1 (SIRT1) deacetylates and inhibits FOXO1 activity; FHL2 enhances the FOXO1-SIRT1 interaction and subsequent FOXO1 deacetylation.

Conclusions:

  • FHL2 inhibits FOXO1 activity in prostate cancer cells.
  • This inhibition is mediated by FHL2 promoting the deacetylation of FOXO1 by SIRT1.
  • The FHL2-SIRT1-FOXO1 axis represents a potential therapeutic target in prostate cancer.

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