O-GlcNAcylation in Chronic Lymphocytic Leukemia and Other Blood Cancers

In the past decade, aberrant O-GlcNAcylation has emerged as a new hallmark of cancer. O-GlcNAcylation is a post-translational modification that results when the amino-sugar β-D-N-acetylglucosamine (GlcNAc) is made in the hexosamine biosynthesis pathway (HBP) and covalently attached to serine and thr...

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Autor principal:	David E. Spaner
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	O-GlcNAc transferase (OGT) O-GlcNAcase (OGase) cancer metabolism chronic lymphocytic leukemia signal transduction Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/35985a96ef4643f581a18cb1fa8a498e
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spelling	oai:doaj.org-article:35985a96ef4643f581a18cb1fa8a498e2021-11-18T09:54:53ZO-GlcNAcylation in Chronic Lymphocytic Leukemia and Other Blood Cancers1664-322410.3389/fimmu.2021.772304https://doaj.org/article/35985a96ef4643f581a18cb1fa8a498e2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.772304/fullhttps://doaj.org/toc/1664-3224In the past decade, aberrant O-GlcNAcylation has emerged as a new hallmark of cancer. O-GlcNAcylation is a post-translational modification that results when the amino-sugar β-D-N-acetylglucosamine (GlcNAc) is made in the hexosamine biosynthesis pathway (HBP) and covalently attached to serine and threonine residues in intracellular proteins by the glycosyltransferase O-GlcNAc transferase (OGT). O-GlcNAc moieties reflect the metabolic state of a cell and are removed by O-GlcNAcase (OGA). O-GlcNAcylation affects signaling pathways and protein expression by cross-talk with kinases and proteasomes and changes gene expression by altering protein interactions, localization, and complex formation. The HBP and O-GlcNAcylation are also recognized to mediate survival of cells in harsh conditions. Consequently, O-GlcNAcylation can affect many of the cellular processes that are relevant for cancer and is generally thought to promote tumor growth, disease progression, and immune escape. However, recent studies suggest a more nuanced view with O-GlcNAcylation acting as a tumor promoter or suppressor depending on the stage of disease or the genetic abnormalities, proliferative status, and state of the p53 axis in the cancer cell. Clinically relevant HBP and OGA inhibitors are already available and OGT inhibitors are in development to modulate O-GlcNAcylation as a potentially novel cancer treatment. Here recent studies that implicate O-GlcNAcylation in oncogenic properties of blood cancers are reviewed, focusing on chronic lymphocytic leukemia and effects on signal transduction and stress resistance in the cancer microenvironment. Therapeutic strategies for targeting the HBP and O-GlcNAcylation are also discussed.David E. SpanerDavid E. SpanerDavid E. SpanerDavid E. SpanerDavid E. SpanerFrontiers Media S.A.articleO-GlcNAc transferase (OGT)O-GlcNAcase (OGase)cancermetabolismchronic lymphocytic leukemiasignal transductionImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	O-GlcNAc transferase (OGT) O-GlcNAcase (OGase) cancer metabolism chronic lymphocytic leukemia signal transduction Immunologic diseases. Allergy RC581-607
spellingShingle	O-GlcNAc transferase (OGT) O-GlcNAcase (OGase) cancer metabolism chronic lymphocytic leukemia signal transduction Immunologic diseases. Allergy RC581-607 David E. Spaner David E. Spaner David E. Spaner David E. Spaner David E. Spaner O-GlcNAcylation in Chronic Lymphocytic Leukemia and Other Blood Cancers
description	In the past decade, aberrant O-GlcNAcylation has emerged as a new hallmark of cancer. O-GlcNAcylation is a post-translational modification that results when the amino-sugar β-D-N-acetylglucosamine (GlcNAc) is made in the hexosamine biosynthesis pathway (HBP) and covalently attached to serine and threonine residues in intracellular proteins by the glycosyltransferase O-GlcNAc transferase (OGT). O-GlcNAc moieties reflect the metabolic state of a cell and are removed by O-GlcNAcase (OGA). O-GlcNAcylation affects signaling pathways and protein expression by cross-talk with kinases and proteasomes and changes gene expression by altering protein interactions, localization, and complex formation. The HBP and O-GlcNAcylation are also recognized to mediate survival of cells in harsh conditions. Consequently, O-GlcNAcylation can affect many of the cellular processes that are relevant for cancer and is generally thought to promote tumor growth, disease progression, and immune escape. However, recent studies suggest a more nuanced view with O-GlcNAcylation acting as a tumor promoter or suppressor depending on the stage of disease or the genetic abnormalities, proliferative status, and state of the p53 axis in the cancer cell. Clinically relevant HBP and OGA inhibitors are already available and OGT inhibitors are in development to modulate O-GlcNAcylation as a potentially novel cancer treatment. Here recent studies that implicate O-GlcNAcylation in oncogenic properties of blood cancers are reviewed, focusing on chronic lymphocytic leukemia and effects on signal transduction and stress resistance in the cancer microenvironment. Therapeutic strategies for targeting the HBP and O-GlcNAcylation are also discussed.
format	article
author	David E. Spaner David E. Spaner David E. Spaner David E. Spaner David E. Spaner
author_facet	David E. Spaner David E. Spaner David E. Spaner David E. Spaner David E. Spaner
author_sort	David E. Spaner
title	O-GlcNAcylation in Chronic Lymphocytic Leukemia and Other Blood Cancers
title_short	O-GlcNAcylation in Chronic Lymphocytic Leukemia and Other Blood Cancers
title_full	O-GlcNAcylation in Chronic Lymphocytic Leukemia and Other Blood Cancers
title_fullStr	O-GlcNAcylation in Chronic Lymphocytic Leukemia and Other Blood Cancers
title_full_unstemmed	O-GlcNAcylation in Chronic Lymphocytic Leukemia and Other Blood Cancers
title_sort	o-glcnacylation in chronic lymphocytic leukemia and other blood cancers
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/35985a96ef4643f581a18cb1fa8a498e
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O-GlcNAcylation in Chronic Lymphocytic Leukemia and Other Blood Cancers

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