SETD6 is a negative regulator of oxidative stress response

Biochimica Et Biophysica Acta
Ayelet ChenDan Levy

Abstract

The protein methyltransferase SETD6 is a key regulator of proliferation and inflammatory processes. However, the role of SETD6 in the regulation of additional cell signaling pathways has not been well studied. Here we show that SETD6 is a negative regulator of the oxidative stress response. Depletion of SETD6 from cells results in elevated Nrf2 levels and a significant increase in Nrf2 antioxidant target gene expression. Using proteomic tools, we uncovered a novel interaction between SETD6 and the oxidative stress sensor DJ1, a protein required for Nrf2-dependent transcription of antioxidant target genes. We show that SETD6 binds DJ1 both in-vitro and in cells but does not methylate DJ1. Under basal conditions, SETD6 and DJ1 are associated at chromatin. Through this interaction, SETD6 inhibits DJ1 activity, which in turn leads to the repression of Nrf2-dependent transcription. In response to oxidative stress, the transcription of Nrf2 antioxidant genes increases. We here show that under this condition, SETD6 mRNA and protein levels are reduced, leading to elevation in Nrf2 expression level and to a weaken interaction between SETD6 and DJ1 at chromatin. Taken together, these findings demonstrate that SETD6 negatively regulates t...Continue Reading

References

Feb 13, 1997·Biochemical and Biophysical Research Communications·D NagakuboH Ariga
Jul 31, 2001·The Journal of Biological Chemistry·K TakahashiH Ariga
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Dec 14, 2004·Biochimie·Delphine EberléFabienne Foufelle
Mar 16, 2005·Cancer Cell·Raymond H KimTak W Mak
Oct 18, 2005·The Journal of Biological Chemistry·Wenbo Zhou, Curt R Freed
Jan 7, 2006·Nucleic Acids Research·Joel D NelsonKarol Bomsztyk
Mar 7, 2006·The Journal of Biological Chemistry·Joungil ChoiLian Li
Oct 4, 2006·Proceedings of the National Academy of Sciences of the United States of America·Casey M ClementsJenny P-Y Ting
Feb 27, 2007·Oncogene·T Pawson, N Warner
Apr 5, 2007·Nature Protocols·Joel D NelsonKarol Bomsztyk
Jun 17, 2008·American Journal of Respiratory and Critical Care Medicine·Deepti MalhotraShyam Biswal
Nov 26, 2010·The Journal of Biological Chemistry·R Sean McNallyJenny P-Y Ting
Apr 5, 2012·Nature Reviews. Genetics·Eric L Greer, Yang Shi
Apr 12, 2012·Human Molecular Genetics·Joo-Young ImM Maral Mouradian
Aug 9, 2012·Human Molecular Genetics·Alvin P JoselinDavid S Park
Nov 15, 2012·Molecular and Cellular Biology·Izumi KatoHiroyoshi Ariga
Dec 12, 2012·Biochemical Pharmacology·Holly K BryanB Kevin Park
Sep 12, 2013·Redox Biology·Emilia KansanenAnna-Liisa Levonen
Feb 8, 2014·British Journal of Cancer·I A IsmailS-H Hong
Apr 23, 2014·Epigenetics : Official Journal of the DNA Methylation Society·Daniel J O'NeillOlivier Binda
Nov 8, 2014·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Min Sik ChoiStuart A Lipton
Apr 4, 2015·Nature Communications·Oren MoscovitzMichal Sharon

❮ Previous
Next ❯

Citations

Mar 5, 2016·Data in Brief·Ofir CohnDan Levy
Nov 16, 2016·Scientific Reports·Ofir CohnDan Levy
Oct 4, 2017·Human Molecular Genetics·Lorena Martín-MoralesDan Levy
Nov 20, 2016·Applied and Environmental Microbiology·Macario Osorio-ConcepciónSergio Casas-Flores
Oct 20, 2019·The Journal of Biological Chemistry·Pengfei LiuAikseng Ooi
Feb 13, 2018·Oncotarget·Michal Feldman, Dan Levy
Aug 22, 2020·American Journal of Physiology. Heart and Circulatory Physiology·Marta W SzulikSarah Franklin
Jan 10, 2019·Proceedings of the National Academy of Sciences of the United States of America·Michal FeldmanDan Levy
Apr 24, 2021·Asian Journal of Psychiatry·Dhruva IthalSanjeev Jain

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.