O-GlcNAc stabilizes SMAD4 by inhibiting GSK-3β-mediated proteasomal degradation.

Scientific Reports
Yeon Jung KimJin Won Cho

Abstract

O-linked β-N-acetylglucosamine (O-GlcNAc) is a post-translational modification which occurs on the hydroxyl group of serine or threonine residues of nucleocytoplasmic proteins. It has been reported that the presence of this single sugar motif regulates various biological events by altering the fate of target proteins, such as their function, localization, and degradation. This study identified SMAD4 as a novel O-GlcNAc-modified protein. SMAD4 is a component of the SMAD transcriptional complex, a major regulator of the signaling pathway for the transforming growth factor-β (TGF-β). TGF-β is a powerful promoter of cancer EMT and metastasis. This study showed that the amount of SMAD4 proteins changes according to cellular O-GlcNAc levels in human lung cancer cells. This observation was made based on the prolonged half-life of SMAD4 proteins. The mechanism behind this interaction was that O-GlcNAc impeded interactions between SMAD4 and GSK-3β which promote proteasomal degradation of SMAD4. In addition, O-GlcNAc modification on SMAD4 Thr63 was responsible for stabilization. As a result, defects in O-GlcNAcylation on SMAD4 Thr63 attenuated the reporter activity of luciferase, the TGF-β-responsive SMAD binding element (SBE). This stud...Continue Reading

References

May 9, 1995·Proceedings of the National Academy of Sciences of the United States of America·T Y ChouG W Hart
Mar 10, 1995·The Journal of Biological Chemistry·C Y LiJ B Little
Aug 1, 1996·Diabetes·D A McClain, E D Crook
May 26, 1999·Proceedings of the National Academy of Sciences of the United States of America·C LiuX He
Aug 22, 2002·Nature Reviews. Cancer·Jean Paul Thiery
Mar 5, 2003·Biochemical and Biophysical Research Communications·Lance WellsGerald W Hart
Jul 16, 2003·Proceedings of the National Academy of Sciences of the United States of America·Anita B Roberts, Lalage M Wakefield
Dec 17, 2003·Cell·Fengxue ZhangJeffrey E Kudlow
Feb 28, 2004·The Journal of Biological Chemistry·Mei WanXu Cao
Dec 1, 2005·Science's STKE : Signal Transduction Knowledge Environment·Dona C Love, John A Hanover
Jan 21, 2009·Cell Research·Jian XuRik Derynck
May 23, 2009·Science·Matthew G Vander HeidenCraig B Thompson
Oct 21, 2010·The EMBO Journal·Sang Yoon ParkJin Won Cho
Jan 22, 2011·Current Opinion in Genetics & Development·Gareth J Inman
Aug 19, 2011·Nature Reviews. Cancer·Chad Slawson, Gerald W Hart
Jan 26, 2012·The Journal of Biological Chemistry·Thomas P LynchMauricio J Reginato
Jun 21, 2012·Cancer Metastasis Reviews·Yvette Drabsch, Peter ten Dijke
Jul 10, 2013·Amino Acids·Zhiyuan Ma, Keith Vosseller
Aug 22, 2013·Frontiers in Endocrinology·Yann FardiniTarik Issad
Oct 23, 2013·Analytical Chemistry·Julien Jean Pierre MauryAndre Boon-Hwa Choo
Feb 11, 2014·Journal of the National Cancer Institute·Daniel R PrincipePaul J Grippo
Feb 21, 2014·American Journal of Physiology. Cell Physiology·Hugo AguilarIsrael Ramirez-Sanchez
Feb 22, 2014·Nature Reviews. Molecular Cell Biology·Samy LamouilleRik Derynck
Apr 20, 2014·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Stéphanie Olivier-Van StichelenTony Lefebvre
Jun 4, 2014·Mediators of Inflammation·Joanna Magdalena Zarzynska
Jun 12, 2014·Frontiers in Oncology·Rafaela Muniz de QueirozWagner Barbosa Dias
Apr 30, 2016·The Journal of Biological Chemistry·Miguel C LucenaWagner B Dias
Aug 19, 2017·Scientific Reports·Ambika KrishnankuttyShin-Ichi Hisanaga

❮ Previous
Next ❯

Methods Mentioned

BETA
transfection
co-immunoprecipitation
immunoprecipitation
immunoprecipitation assay
affinity purification
ubiquitination
PCR
Assay

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.

Related Papers

Biochemical and Biophysical Research Communications
Jinghua YanQinong Ye
Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Danielle LangeveldLodewijk A A Brosens
© 2021 Meta ULC. All rights reserved