Characterization of the O-GlcNAc protein modification in Xenopus laevis oocyte during oogenesis and progesterone-stimulated maturation

Slawson, Chad; Shafii, Susan M.; Amburgey, James E.; Potter, Robert

doi:10.1016/s0304-4165(02)00369-0

Cited by 35 publications

(32 citation statements)

References 44 publications

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“…Microinjection of galactosyltransferase an enzyme that caps terminal N-acetyL-glucosamine preventing OGA removal of the sugar moiety induces maturation defects causing mitotic checkpoint activation and cell death. 9 Oocytes treated with OGA inhibitor PUGNAc failed to mature properly, 10 while microinjection of GlcNAc impaired maturation and spindle formation. 11 Additionally, inhibition of OGT blocks the G 2 /M transition during maturation, 12 but microinjection of OGT promotes entry into M phase.…”

Section: Introductionmentioning

confidence: 98%

Reduced O-GlcNAcase expression promotes mitotic errors and spindle defects

et al. 2016

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Alterations in O-GlcNAc cycling, the addition and removal of O-GlcNAc, lead to mitotic defects and increased aneuploidy. Herein, we generated stable O-GlcNAcase (OGA, the enzyme that removes OGlcNAc) knockdown HeLa cell lines and characterized the effect of the reduction in OGA activity on cell cycle progression. After release from G 1 /S, the OGA knockdown cells progressed normally through S phase but demonstrated mitotic exit defects. Cyclin A was increased in the knockdown cells while Cyclin B and D expression was reduced. Retinoblastoma protein (RB) phosphorylation was also increased in the knockdown compared to control. At M phase, the knockdown cells showed more compact spindle chromatids than control cells and had a greater percentage of cells with multipolar spindles. Furthermore, the timing of the inhibitory tyrosine phosphorylation of Cyclin Dependent Kinase 1 (CDK1) was altered in the OGA knockdown cells. Although expression and localization of the chromosomal passenger protein complex (CPC) was unchanged, histone H3 threonine 3 phosphorylation was decreased in one of the OGA knockdown cell lines. The Ewing Sarcoma Breakpoint Region 1 Protein (EWS) participates in organizing the CPC at the spindle and is a known substrate for O-GlcNAc transferase (OGT, the enzyme that adds OGlcNAc). EWS O-GlcNAcylation was significantly increased in the OGA knockdown cells promoting uneven localization of the mitotic midzone. Our data suggests that O-GlcNAc cycling is an essential mechanism for proper mitotic signaling and spindle formation, and alterations in the rate of O-GlcNAc cycling produces aberrant spindles and promotes aneuploidy.

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Section: Introductionmentioning

confidence: 98%

Reduced O-GlcNAcase expression promotes mitotic errors and spindle defects

et al. 2016

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“…The following observations support the notion that OGlcNAc is a regulatory post-translational modification analogous to protein phosphorylation: 1) O-GlcNAc is not further extended into more complex oligo-or polysaccharides with the exception of plant nuclear pore proteins (62,162); 2) the half-life of the O-GlcNAc modification is shorter that that of the protein it modifies (38,86,144); 3) O-GlcNAc levels respond dynamically to both extracellular (e.g., insulin) and intracellular (e.g., stress) stimuli (12,13,22,38,53,74,91,118,153,188,195); 4) sites of O-GlcNAc modification are similar to those used by protein kinases and are identical to those used by kinases on a subset of proteins (57); 5) OGlcNAc is essential for life in mammals, arabidopsis and drosophila (45,59,131,146,149), and the deletion of the O-GlcNAc transferase (OGT) is lethal in mice [embryonic day (E) 4.5] cells and some tissues (131,146); and 6) numerous studies have implicated O-GlcNAc in regulating enzyme activity, DNA binding, protein binding, localization, half-life, and regulating phosphorylation levels either by regulating protein kinases or by blocking amino acids that would otherwise be phosphorylated (58). For a subset of proteins, OGlcNAc can block phosphorylation either by modifying the same Ser/Thr residue that would usually be modified (e.g., C-Myc, Thr 58) (23,24), or sterically by modifying a nearby Ser/Thr residue (e.g., casein kinase 2, Ser347).…”

Section: Introductionmentioning

confidence: 99%

The roles ofO-linked β-N-acetylglucosamine in cardiovascular physiology and disease

Zachara

2012

American Journal of Physiology-Heart and Circulatory Physiology

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More than 1,000 proteins of the nucleus, cytoplasm, and mitochondria are dynamically modified by O-linked β- N-acetylglucosamine ( O-GlcNAc), an essential post-translational modification of metazoans. O-GlcNAc, which modifies Ser/Thr residues, is thought to regulate protein function in a manner analogous to protein phosphorylation and, on a subset of proteins, appears to have a reciprocal relationship with phosphorylation. Like phosphorylation, O-GlcNAc levels change dynamically in response to numerous signals including hyperglycemia and cellular injury. Recent data suggests that O-GlcNAc appears to be a key regulator of the cellular stress response, the augmentation of which is protective in models of acute vascular injury, trauma hemorrhage, and ischemia-reperfusion injury. In contrast to these studies, O-GlcNAc has also been implicated in the development of hypertension and type II diabetes, leading to vascular and cardiac dysfunction. Here we summarize the current understanding of the roles of O-GlcNAc in the heart and vasculature.

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“…Both OGT and O-GlcNAcase have been found in complexes with phosphatases and kinases, suggesting that the exchange between phosphorylation and GlcNAcylation is rapid and dynamic (21,(25)(26)(27). Similar to phosphorylation, O-GlcNAc is dynamically added and removed in response to numerous extracellular signals, including: extracellular glucose concentration (28 -30), cell cycle (31), development (32,33), hormones such as insulin (34,35), phorbol esters (36), and the focus of this study, cellular stress (37).…”

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O-Linked β-N-acetylglucosamine (O-GlcNAc) Regulates Stress-induced Heat Shock Protein Expression in a GSK-3β-dependent Manner

Kazemi

Chang

Haserodt

et al. 2010

Journal of Biological Chemistry

159

214

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To investigate the mechanisms by which O-linked ␤-Nacetylglucosamine modification of nucleocytoplasmic proteins (O-GlcNAc) confers stress tolerance to multiple forms of cellular injury, we explored the role(s) of O-GlcNAc in the regulation of heat shock protein (HSP) expression. Using a cell line in which deletion of the O-GlcNAc transferase (OGT; the enzyme that adds O-GlcNAc) can be induced by 4-hydroxytamoxifen, we screened the expression of 84 HSPs using quantitative reverse transcriptase PCR. In OGT null cells the stressinduced expression of 18 molecular chaperones, including HSP72, were reduced. GSK-3␤ promotes apoptosis through numerous pathways, including phosphorylation of heat shock factor 1 (HSF1) at Ser 303 (Ser(P) 303 HSF1), which inactivates HSF1 and inhibits HSP expression. In OGT null cells we observed increased Ser(P) 303 HSF1; conversely, in cells in which O-GlcNAc levels had been elevated, reduced Ser(P) 303 HSF1 was detected. These data, combined with those showing that inhibition of GSK-3␤ in OGT null cells recovers HSP72 expression, suggests that O-GlcNAc regulates the activity of GSK-3␤. In OGT null cells, stress-induced inactivation of GSK-3␤ by phosphorylation at Ser 9 was ablated providing a molecular basis for these findings. Together, these data suggest that stress-induced GlcNAcylation increases HSP expression through inhibition of GSK-3␤.

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Characterization of the O-GlcNAc protein modification in Xenopus laevis oocyte during oogenesis and progesterone-stimulated maturation

Cited by 35 publications

References 44 publications

Reduced O-GlcNAcase expression promotes mitotic errors and spindle defects

Reduced O-GlcNAcase expression promotes mitotic errors and spindle defects

The roles ofO-linked β-N-acetylglucosamine in cardiovascular physiology and disease

O-Linked β-N-acetylglucosamine (O-GlcNAc) Regulates Stress-induced Heat Shock Protein Expression in a GSK-3β-dependent Manner

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