Glycosylation of Nucleocytoplasmic Proteins: Signal Transduction and O-GlcNAc

Wells, Lance; Vosseller, Keith; Hart, Gerald W.

doi:10.1126/science.1058714

Cited by 881 publications

(683 citation statements)

References 27 publications

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“…This enzyme modifies a wide variety of proteins, including cytoskeletal proteins and signal transduction and transcription factors. It mediates a novel glycan-dependent signalling pathway that has a dynamic interaction with phosphorylation (Wells et al, 2001), and although it is found in many organisms, its role in early development has not yet been investigated. 17D4 RNA is detected weakly throughout X. tropicalis neurula embryos with enhanced staining in the neural tube (Fig.…”

Section: D4 (Truncated)mentioning

confidence: 99%

Pilot morpholino screen in Xenopus tropicalis identifies a novel gene involved in head development

Kenwrick¹,

Amaya

Papalopulu

2003

Developmental Dynamics

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The diploid frog X. tropicalis has recently been adopted as a model genetic system, but loss-of-function screens in Xenopus have not yet been performed. We have undertaken a pilot functional knockdown screen in X. tropicalis for genes involved in nervous system development by injecting antisense morpholino (MO) oligos directed against X. tropicalis mRNAs. Twenty-six genes with primary expression in the nervous system were selected as targets based on an expression screen previously conducted in X. laevis. Reproducible phenotypes were observed for six and for four of these, a second MO gave a similar result. One of these genes encodes a novel protein with previously unknown function. Knocking down this gene, designated pinhead, results in severe microcephaly, whereas, overexpression results in macrocephaly. Together with the early embryonic expression in the anterior neural plate, these data indicate that pinhead is a novel gene involved in controlling head development. Developmental Dynamics 229:289 -299, 2004.

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Section: D4 (Truncated)mentioning

confidence: 99%

Pilot morpholino screen in Xenopus tropicalis identifies a novel gene involved in head development

Kenwrick¹,

Amaya

Papalopulu

2003

Developmental Dynamics

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“…[1][2][3] O-GlcNAc is abundant in the brain, particularly on cytoskeletal proteins, [4][5] which has supported hypothesis that disruptions of OGlcNAc proteins may contribute to certain neurodegenerative disorders such as Parkinson dystonia 6 and Alzheimer's disease. 5 O-GlcNAc is also present in many transcription regulatory proteins.…”

Section: Introductionmentioning

confidence: 99%

A Quantum Mechanics/Molecular Mechanics Study of the Protein−Ligand Interaction of Two Potent Inhibitors of Human O-GlcNAcase: PUGNAc and NAG-Thiazoline

et al. 2008

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“…Like phosphorylation, O-GlcNAcylation is a dynamic modification. Virtually every reported OGT substrate is also a phosphoprotein, making them all potentially affected by crosstalk (8). Initially, reciprocal interplay, whereby phosphorylation and O-GlcNAcylation occur on the same Ser/Thr site, was suggested as a major crosstalk mechanism (9).…”

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confidence: 99%

Elucidating crosstalk mechanisms between phosphorylation and O-GlcNAcylation

Leney

Atmioui

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

128

127

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Proteins can be modified by multiple posttranslational modifications (PTMs), creating a PTM code that controls the function of proteins in space and time. Unraveling this complex PTM code is one of the great challenges in molecular biology. Here, using mass spectrometry-based assays, we focus on the most common PTMs-phosphorylation and O-GlcNAcylation-and investigate how they affect each other. We demonstrate two generic crosstalk mechanisms. First, we define a frequently occurring, very specific and stringent phosphorylation/ O-GlcNAcylation interplay motif, (pSp/T)P(V/A/T)(gS/gT), whereby phosphorylation strongly inhibits O-GlcNAcylation. Strikingly, this stringent motif is substantially enriched in the human (phospho)proteome, allowing us to predict hundreds of putative O-GlcNAc transferase (OGT) substrates. A set of these we investigate further and show them to be decent substrates of OGT, exhibiting a negative feedback loop when phosphorylated at the P-3 site. Second, we demonstrate that reciprocal crosstalk does not occur at PX(S/T)P sites, i.e., at sites phosphorylated by proline-directed kinases, which represent 40% of all sites in the vertebrate phosphoproteomes.O-GlcNAcylation | phosphorylation | crosstalk | signaling | regulation

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Glycosylation of Nucleocytoplasmic Proteins: Signal Transduction and O-GlcNAc

Cited by 881 publications

References 27 publications

Pilot morpholino screen in Xenopus tropicalis identifies a novel gene involved in head development

Pilot morpholino screen in Xenopus tropicalis identifies a novel gene involved in head development

A Quantum Mechanics/Molecular Mechanics Study of the Protein−Ligand Interaction of Two Potent Inhibitors of Human O-GlcNAcase: PUGNAc and NAG-Thiazoline

Elucidating crosstalk mechanisms between phosphorylation and O-GlcNAcylation

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