Characterization of O-GlcNAc cycling and proteomic identification of differentially O-GlcNAcylated proteins during G1/S transition

Drougat, Ludivine; Stichelen, Stéphanie Olivier-Van; Mortuaire, Marlène; Foulquier, François; Lacoste, Anne-Sophie; Michalski, Jean‐Claude; Lefebvre, Tony; Vercoutter‐Edouart, Anne‐Sophie

doi:10.1016/j.bbagen.2012.08.024

Cited by 57 publications

(65 citation statements)

References 47 publications

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“…O-glycosylation of A-type lamins on at least 4 serine or threonine residues [35][36][37] could interfere with lamin polymerization as already seen for other intermediate filaments [38] and has been shown to vary during cell cycle [39].…”

Section: Other Post-translational Modifications Of Laminsmentioning

confidence: 99%

Nuclear matrix, nuclear envelope and premature aging syndromes in a translational research perspective

Cau

Navarro

Harhouri

et al. 2014

Seminars in Cell & Developmental Biology

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Lamin A-related progeroid syndromes are genetically determined, extremely rare and severe. In the past ten years, our knowledge and perspectives for these diseases has widely progressed, through the progressive dissection of their pathophysiological mechanisms leading to precocious and accelerated aging, from the genes mutations discovery until therapeutic trials in affected children. A-type lamins are major actors in several structural and functional activities at the nuclear periphery, as they are major components of the nuclear lamina. However, while this is usually poorly considered, they also play a key role within the rest of the nucleoplasm, whose defects are related to cell senescence. Although nuclear shape and nuclear envelope deformities are obvious and visible events, nuclear matrix disorganization and abnormal composition certainly represent the most important causes of cell defects with dramatic pathological consequences. Therefore, lamin-associated diseases should be better referred as laminopathies instead of envelopathies, this later being too restrictive, considering neither the key structural and functional roles of soluble lamins in the entire nucleoplasm, nor the nuclear matrix contribution to the pathophysiology of lamin-associated disorders and in particular in defective lamin A processing-associated aging diseases. Based on both our understanding of pathophysiological mechanisms and the biological and clinical consequences of progeria and related diseases, therapeutic trials have been conducted in patients and were terminated less than 10 years after the gene discovery, a quite fast issue for a genetic disease. Pharmacological drugs have been repurposed and used to decrease the toxicity of the accumulated, unprocessed and truncated prelaminA in progeria. To date, none of them may be considered as a cure for progeria and these clinical strategies were essentially designed toward reducing a subset of the most dramatic and morbid features associated to progeria. New therapeutic strategies under study, in particular targeting the protein expression pathway at the mRNA level, have shown a remarkable efficacy both in vitro in cells and in vivo in mice models. Strategies intending to clear the toxic accumulated proteins from the nucleus are also under evaluation. However, although exceedingly rare, improving our knowledge of genetic progeroid syndromes and searching for innovative and efficient therapies in these syndromes is of paramount importance as, even before they can be used to save lives, they may significantly (i) expand the affected childrens' lifespan and preserve their quality of life; (ii) improve our understanding of aging-related disorders and other more common diseases; and (iii) expand our fundamental knowledge of physiological aging and its links with major physiological processes such as those involved in oncogenesis.

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Section: Other Post-translational Modifications Of Laminsmentioning

confidence: 99%

Nuclear matrix, nuclear envelope and premature aging syndromes in a translational research perspective

Cau

Navarro

Harhouri

et al. 2014

Seminars in Cell & Developmental Biology

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“…Generally, changes in OGA protein levels are more pronounced relative to OGT. Moreover, OGA activity is also increased in the S-phase, which is consistent with the reduction in O-GlcNAcylation [24]. Glucosamine (GlcN) supplementation elevates O-GlcNAcylation.…”

Section: O-glcnac Cycling In Interphasementioning

confidence: 61%

“…Interestingly, like phosphorylation, O-GlcNAcylation is regulated as metazoan cells progress through interphase. First, levels of O -GlcNAc on nuclear and cytoplasmic proteins rise when cells progress into the G 1 phase [24,25], but decrease rapidly when cells enter the S-phase [24]. Both OGT and OGA protein levels increase as the cells progress through the S-phase [24].…”

Section: O-glcnac Cycling In Interphasementioning

confidence: 99%

The sweet side of the cell cycle

Tan

Duncan

Slawson

2017

Biochemical Society Transactions

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Cell division (mitosis) and gamete production (meiosis) are fundamental requirements for normal organismal development. The mammalian cell cycle is tightly regulated by different checkpoints ensuring complete and precise chromosomal segregation and duplication. In recent years, researchers have become increasingly interested in understanding how O-GlcNAc regulates the cell cycle. The O-GlcNAc post-translation modification is an O-glycosidic bond of a single β-N-acetylglucosamine sugar to serine/threonine residues of intracellular proteins. This modification is sensitive toward changes in nutrient levels in the cellular environment making O-GlcNAc a nutrient sensor capable of influencing cell growth and proliferation. Numerous studies have established that O-GlcNAcylation is essential in regulating mitosis and meiosis, while loss of O-GlcNAcylation is lethal in growing cells. Moreover, aberrant O-GlcNAcylation is linked with cancer and chromosomal segregation errors. In this review, we will discuss how O-GlcNAc controls different aspects of the cell cycle with a particular emphasis on mitosis and meiosis.

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“…As mentioned above, the O -GlcNAc cycling enzymes OGT and OGA tightly regulate the level of O -GlcNAcylation. Enhanced O -GlcNAcylation level corresponding to increased OGT and decreased OGA expression is commonly observed in various cancers including bone (41), bladder (42), breast (26, 43–45), bile duct (46), colon (47–49), leukemia (50), liver (51), lung (47), ovary (36), pancreas (30), and prostate (52, 53). Alteration of this glycosylation in thyroid cancer, however, occurs in the opposite way (54).…”

Section: Regulation Of O-glcnac Cycling Enzymes and O-glcnacylationmentioning

confidence: 99%

Aberrant O-GlcNAcylated Proteins: New Perspectives in Breast and Colorectal Cancer

et al. 2014

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Increasing glucose consumption is thought to provide an evolutionary advantage to cancer cells. Alteration of glucose metabolism in cancer influences various important metabolic pathways including the hexosamine biosynthesis pathway (HBP), a relatively minor branch of glycolysis. Uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), an end product of HBP, is a sugar substrate used for classical glycosylation and O-GlcNAcylation, a post-translational protein modification implicated in a wide range of effects on cellular functions. Emerging evidence reveals that certain cellular proteins are abnormally O-GlcNAc modified in many kinds of cancers, indicating O-GlcNAcylation is associated with malignancy. Since O-GlcNAc rapidly on and off modifies in a similar time scale as in phosphorylation and these modifications may occur on proteins at either on the same or adjacent sites, it suggests that both modifications can work to regulate the cellular signaling pathways. This review describes the metabolic shifts related to the HBP, which are commonly found in most cancers. It also describes O-GlcNAc modified proteins identified in primary breast and colorectal cancer, as well as in the related cancer cell lines. Moreover, we also discuss the potential use of aberrant O-GlcNAcylated proteins as novel biomarkers of cancer.

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Characterization of O-GlcNAc cycling and proteomic identification of differentially O-GlcNAcylated proteins during G1/S transition

Cited by 57 publications

References 47 publications

Nuclear matrix, nuclear envelope and premature aging syndromes in a translational research perspective

Nuclear matrix, nuclear envelope and premature aging syndromes in a translational research perspective

The sweet side of the cell cycle

Aberrant O-GlcNAcylated Proteins: New Perspectives in Breast and Colorectal Cancer

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