Gcn5 Modulates the Cellular Response to Oxidative Stress and Histone Deacetylase Inhibition

Journal of Cellular Biochemistry
Ann-Christin GaupelMartin Tenniswood

Abstract

To identify chemical genetic interactions underlying the mechanism of action of histone deacetylase inhibitors (HDACi) a yeast deletion library was screened for hypersensitive deletion mutants that confer increased sensitivity to the HDACi, CG-1521. The screen demonstrated that loss of GCN5 or deletion of components of the Gcn5 histone acetyltransferase (HAT) complex, SAGA, sensitizes yeast to CG-1521-induced cell death. Expression profiling after CG-1521 treatment reveals increased expression of genes involved in metabolism and oxidative stress response, and oxidative stress response mutants are hypersensitive to CG-1521 treatment. Accumulation of reactive oxygen species and increased cell death are enhanced in the gcn5Δ deletion mutant, and are abrogated by anti-oxidants, indicating a central role of oxidative stress in CG-1521-induced cell death. In human cell lines, siRNA mediated knockdown of GCN5 or PCAF, or chemical inhibition of GCN5 enzymatic activity, increases the sensitivity to CG-1521 and SAHA. These data suggest that the combination of HDAC and GCN5/PCAF inhibitors can be used for cancer treatment.

References

Dec 9, 1998·Proceedings of the National Academy of Sciences of the United States of America·M B EisenD Botstein
Sep 22, 1999·Molecular and Cellular Biology·A EberharterJ L Workman
Oct 12, 2000·Proceedings of the National Academy of Sciences of the United States of America·T YamauchiY Nakatani
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Aug 22, 2002·Proceedings of the National Academy of Sciences of the United States of America·Lisa M ButlerVictoria M Richon
Jan 8, 2005·Proceedings of the National Academy of Sciences of the United States of America·J S UngerstedtP A Marks
Jan 12, 2005·The Biochemical Journal·Caryn E OuttenValeria C Culotta
Jul 11, 2006·The Journal of Biological Chemistry·Koichi OkumuraFrank B Furnari
Jul 9, 2008·Proceedings of the National Academy of Sciences of the United States of America·R B ParmigianiP A Marks
Jul 7, 2009·Drug Discovery Today·Frank J Dekker, Hidde J Haisma
Aug 4, 2010·Proceedings of the National Academy of Sciences of the United States of America·J-H LeePaul A Marks
Feb 1, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hidehiko KikuchiTatsuo Nakayama
Feb 2, 2011·Biochemical and Biophysical Research Communications·Hidehiko KikuchiTatsuo Nakayama
Nov 24, 2011·Nucleic Acids Research·J Michael CherryEdith D Wong
Mar 23, 2012·Molecular Biology of the Cell·Michael J MalloryRandy Strich
Aug 27, 2013·Current Biology : CB·Michael DowneyDavid P Toczyski
Nov 5, 2013·Anti-cancer Drugs·Marije SlingerlandHans Gelderblom
Jan 3, 2014·The Journal of Clinical Investigation·Alison C West, Ricky W Johnstone
Jun 28, 2014·BMC Genomics·Ann-Christin GaupelMartin Tenniswood

❮ Previous
Next ❯

Citations

Dec 17, 2017·Immunological Reviews·Khaled KhazimIdan Cohen
Jan 25, 2019·Proceedings of the National Academy of Sciences of the United States of America·Ida Bagus AndikaNobuhiro Suzuki
Feb 20, 2019·Biology Open·Arianna MontanariSilvia Francisci
Jan 11, 2017·Proceedings of the National Academy of Sciences of the United States of America·Xuanye CaoWei Yu
Apr 13, 2017·Proceedings of the National Academy of Sciences of the United States of America·Ida Bagus AndikaNobuhiro Suzuki
Jan 15, 2021·Clinical Science·Md Ezazul HaqueDong-Kug Choi
Jun 9, 2021·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Francesca AntonazziGiorgio Camilloni

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cancer Metabolism: Therapeutic Targets

Targeting the mechanisms by which cancer cells acquire energy for metabolic needs is a therapeutic target. Discover the latest research on cancer metabolism and therapeutic targets.

Related Papers

Nihon yakurigaku zasshi. Folia pharmacologica Japonica
Minoru Yoshida
International Journal of Radiation Oncology, Biology, Physics
Prakash ChinnaiyanPaul M Harari
© 2022 Meta ULC. All rights reserved