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Investigating the role of O-GlcNAc glycosylation in cancer and neurodegenerative disease

Wang, Andrew C. and Yi, Wen and Jensen, Elizabeth H. and Hsieh-Wilson, Linda C. (2013) Investigating the role of O-GlcNAc glycosylation in cancer and neurodegenerative disease. In: 245th ACS National Meeting & Exposition, Abstracts of Papers, April 7-11, 2013, New Orleans, LA.

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The addn. of a single O-linked N-Acetylglucosamine (O-GlcNAc) sugar onto proteins is a ubiquitous and dynamic posttranslational modification that regulates many important biol. processes, including cell signaling, transcription, metab., and memory storage. This intracellular modification has been identified on over a thousand proteins, including histones, RNA polymerase, enzymes involved in glycolysis, amyloid precursor protein, and tau. We are investigating the functional roles of this modification in cancer and neurodegenerative diseases. Our studies have uncovered a unique role for the O-GlcNAc modification in regulating the metabolic state of cancer cells. Specifically, we show that glycosylation of phosphofruktokinase-1 (PFK1) enables cancer cells to acquire a selective growth and survival advantage by increasing metabolic flux through the pentose phosphate pathway. In the brain, the O-GlcNAc modification has been shown to reduce tau hyperphosphorylation, a major hallmark in several neurodegenerative diseases. To better understand the role of O-GlcNAc in the brain, we generated a conditional knockout mice lacking O-GlcNAc transferase (OGT), the single enzyme responsible for the modification. Our findings indicate that loss of OGT induces rapid neurodegeneration, suggesting that a redn. of O-GlcNAc glycosylation may contribute to the pathol. of neurodegenerative diseases.

Item Type:Conference or Workshop Item (Paper)
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URLURL TypeDescription website
Yi, Wen0000-0002-4257-3355
Hsieh-Wilson, Linda C.0000-0001-5661-1714
Additional Information:© 2013 American Chemical Society.
Record Number:CaltechAUTHORS:20130730-092228606
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:39645
Deposited By: Tony Diaz
Deposited On:19 Aug 2013 22:06
Last Modified:09 Mar 2020 13:19

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