Disrupting the enzyme complex regulating O-GlcNAcylation blocks signaling and development

Glycobiology
Thomas R WhisenhuntJeffrey E Kudlow

Abstract

Although the knowledge that nuclear and cytoplasmic proteins are modified with N-acetylglucosamine has existed for decades, little has been shown as to its function until recently. There are now substantial data highlighting the significance of proper regulation of this modification in multiple cellular processes. Currently, only two enzymes are known that regulate this modification. O-GlcNAc transferase (OGT) modifies protein substrates posttranslationally by adding the N-acetylglucosamine. Bifunctional nuclear/cytoplasmic O-GlcNAcase and acetyl transferase (NCOAT) is responsible for cleaving the modification from target proteins. Here, we demonstrate for the first time an unusual association of these two opposing enzymes into a single O-GlcNAczyme complex. NCOAT and OGT associate strongly through specific domains such that NCOAT accompanies OGT, with histone deacetylases (HDACs), into transcription corepression complexes. Exclusion of NCOAT activities from OGT association blocks proper estrogen-dependent cell signaling as well as mammary development in transgenic mice. This demonstrates that NCOAT is in a strategic position to rapidly counteract OGT and HDAC without requiring its recruitment.

References

Nov 1, 1990·Nature·B MossT R Fuerst
Jan 24, 1997·The Journal of Biological Chemistry·M S Jiang, G W Hart
Oct 29, 1997·Molecular and Cellular Biology·M D RoosJ E Kudlow
Apr 16, 1998·Genes & Development·K Struhl
Apr 2, 1999·Cell·S BjörklundK Weiss
Mar 16, 2000·Proceedings of the National Academy of Sciences of the United States of America·K LiuJ E Kudlow
May 9, 2000·Biochemical and Biophysical Research Communications·M D Roos, J A Hanover
May 9, 2001·Biochemical and Biophysical Research Communications·N ComtesseE Meese
May 24, 2001·Proceedings of the National Academy of Sciences of the United States of America·X YangJ E Kudlow
Jun 11, 2002·Biochemical and Biophysical Research Communications·Robert J KonradJeffrey E Kudlow
Nov 6, 2002·Biochimica Et Biophysica Acta·Niall O'Donnell
Jan 23, 2003·Journal of Cell Science·Dona C LoveJarema Kochran
Jul 16, 2003·Molecular and Cellular Biology·Takahiro Ishizuka, Mitchell A Lazar
Dec 17, 2003·Cell·Fengxue ZhangJeffrey E Kudlow
Mar 17, 2004·Proceedings of the National Academy of Sciences of the United States of America·Brian A Van TineLouise T Chow
Jun 16, 2005·Nature Reviews. Molecular Cell Biology·Valentina Perissi, Michael G Rosenfeld

❮ Previous
Next ❯

Citations

Aug 19, 2011·Nature Reviews. Cancer·Chad Slawson, Gerald W Hart
Apr 7, 2010·Proceedings of the National Academy of Sciences of the United States of America·Dona C LoveJohn A Hanover
Nov 8, 2007·Rejuvenation Research·Eija PöllänenVuokko Kovanen
Sep 13, 2006·Molecular and Cellular Biology·Damon B BoweJeffrey E Kudlow
Dec 24, 2010·American Journal of Physiology. Cell Physiology·Ping HuangAndrew J Paterson
Nov 24, 2006·American Journal of Physiology. Endocrinology and Metabolism·Katherine A RobinsonMaria G Buse
May 1, 2008·American Journal of Physiology. Endocrinology and Metabolism·Ronald J CopelandGerald W Hart
Nov 26, 2008·American Journal of Physiology. Heart and Circulatory Physiology·Boglarka LaczyJohn C Chatham
Nov 12, 2010·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Victor V LimaRita C Tostes
Aug 3, 2011·Journal of Cell Science·Chithra N KeembiyehettyJohn A Hanover
Sep 1, 2014·Amino Acids·Alexis K Nagel, Lauren E Ball
Jan 31, 2014·Pflügers Archiv : European journal of physiology·Caroline Cieniewski-BernardBruno Bastide
May 15, 2007·Nature Chemical Biology·Nelly KhidekelLinda C Hsieh-Wilson
Jun 19, 2013·The Journal of Organic Chemistry·Ernest G NolenKristopher V Waynant
Nov 26, 2009·FEBS Letters·Shiuh-Rong HoAndrew J Paterson
Apr 1, 2015·The Journal of Cell Biology·Michelle R Bond, John A Hanover
Dec 11, 2007·Critical Reviews in Biochemistry and Molecular Biology·Jillian R BrownJeffrey D Esko
Aug 12, 2009·Biochimica Et Biophysica Acta·Matthew S Macauley, David J Vocadlo
Aug 4, 2009·Biochimica Et Biophysica Acta·John A HanoverDona C Love
Jul 7, 2009·Biochemical and Biophysical Research Communications·Kai WangAndrew J Paterson
Oct 16, 2014·Clinical and Experimental Medicine·Katarzyna StarskaAnna Krześlak
Apr 7, 2006·Journal of Cellular Biochemistry·Jeffrey E Kudlow
Nov 14, 2012·Current Opinion in Chemical Biology·David J Vocadlo
Sep 25, 2010·The Biochemical Journal·Marianne SchimplDaan M F van Aalten
Jul 22, 2014·Critical Reviews in Biochemistry and Molecular Biology·Eun J KimJohn A Hanover
May 27, 2014·Biochimica Et Biophysica Acta·Sarah FörsterD Allan Butterfield
Sep 29, 2009·The International Journal of Biochemistry & Cell Biology·Brooke D LazarusJohn A Hanover
Jul 25, 2007·Biochemical and Biophysical Research Communications·Céline GuinezTony Lefebvre
Nov 18, 2014·Frontiers in Physiology·Caroline Cieniewski-BernardBruno Bastide
Dec 19, 2014·Frontiers in Endocrinology·Zhen ZhangChad Slawson
Nov 27, 2014·Frontiers in Endocrinology·Parunya ChaiyawatVoraratt Champattanachai
Oct 6, 2016·Cell Reports·Simon HauriChristian Beisel
May 11, 2017·Nature Reviews. Molecular Cell Biology·Xiaoyong Yang, Kevin Qian
Mar 7, 2017·Biochimica Et Biophysica Acta. General Subjects·Hideki NakanishiXiao-Dong Gao

❮ 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.