Protein O-GlcNAcylation regulates Drosophila growth through the insulin signaling pathway

Park, Su‐Jin; Park, Si Hyoung; Baek, Ju Yuel; Jy, Ye Jin; Kim, Kwan Soo; Roth, Jürgen; Cho, Jin Won; Choe, Kwang Min

doi:10.1007/s00018-011-0640-7

Cited by 14 publications

(12 citation statements)

References 28 publications

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“…Some studies have shown that increased O-GlcNAc could dampen the insulin response-inhibiting Akt pathway in insulin target tissues, such as adipocytes and muscle cells (48 -51). However, in other systems it has been demonstrated that an increase in O-GlcNAcylation enhanced insulin signaling (52,53). In line with our data, it has also been shown that preadipocyte differentiation is induced through an increase in O-GlcNAc protein modification (54), whereas adipocyte differentiation can be blocked inhibiting the HBP (55).…”

Section: Discussionsupporting

confidence: 90%

“…A decrease in Akt phosphorylation and/or Akt activity associated with an increase in Akt OGlcNAcylation has been described by some investigators (49,50,62). However, it has also been demonstrated that Akt O-GlcNAcylation did not inhibits its phosphorylation, having no effect or a stimulating effect on its enzymatic activity (42,52,53). Irrespective of the modulation of Akt activity, O-GlcNA- cylation can also modulate the cellular distribution of the enzyme, probably inducing further changes in the enzyme targets (42).…”

Section: Discussionmentioning

confidence: 94%

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The Increase in O-Linked N-Acetylglucosamine Protein Modification Stimulates Chondrogenic Differentiation Both in Vitro and in Vivo

Andrés-Bergós

Tardío

Larrañaga-Vera

et al. 2012

Journal of Biological Chemistry

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 94%

The Increase in O-Linked N-Acetylglucosamine Protein Modification Stimulates Chondrogenic Differentiation Both in Vitro and in Vivo

Andrés-Bergós

Tardío

Larrañaga-Vera

et al. 2012

Journal of Biological Chemistry

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“…More generally, we would like to point out that regulation of O-GlcNAc in D. melanogaster is not governed exclusively by temperature. Indeed, other regulatory inputs are known (24)(25)(26)(27)(28)(29). We would also like to point out that in our analysis of larval extracts (Fig.…”

Section: Test) (B)mentioning

confidence: 86%

O- GlcNAc reports ambient temperature and confers heat resistance on ectotherm development

Radermacher

Myachina

Bosshardt

et al. 2014

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

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Effects of temperature on biological processes are complex. Diffusion is less affected than the diverse enzymatic reactions that have distinct individual temperature profiles. Hence thermal fluctuations pose a formidable challenge to ectothermic organisms in which body temperature is largely dictated by the ambient temperature. How cells in ectotherms cope with the myriad disruptive effects of temperature variation is poorly understood at the molecular level. Here we show that nucleocytoplasmic posttranslational modification of proteins with O-linked GlcNAc (O-GlcNAc) is closely correlated with ambient temperature during development of distantly related ectotherms ranging from the insect Drosophila melanogaster to the nematode Caenorhabditis elegans to the fish Danio rerio. Regulation seems to occur at the level of activity of the only two enzymes, O-GlcNAc transferase and O-GlcNAcase, that add and remove, respectively, this posttranslational modification in nucleus and cytoplasm. With genetic approaches in D. melanogaster and C. elegans, we demonstrate the importance of high levels of this posttranslational modification for successful development at elevated temperatures. Because many cytoplasmic and nuclear proteins in diverse pathways are O-GlcNAc targets, temperature-dependent regulation of this modification might contribute to an efficient coordinate adjustment of cellular processes in response to thermal change.O-GlcNAcylation | temperature acclimation A mbient temperature can fluctuate over various time scales and degrees in different ecological niches. Organisms cope with thermal fluctuations using alternative strategies. Endotherms like humans rely primarily on internally generated heat in combination with intricate regulation for maintenance of a relatively high and constant core body temperature. In contrast, the majority of organisms are ectotherms that produce far less heat. Their internal temperature is primarily dictated by the environment. Cells in some ectotherms are able to acclimate over a remarkable range of ambient temperatures even though temperature change has pervasive effects. All biological processes depend on temperature, but notably not in a uniform manner. Compensation of the myriad disruptive effects of temperature change at the cellular level necessitates extremely complex regulation. Our understanding of the responsible molecular mechanisms is still remarkably poor, even though ambient temperature is often the major ecological determinant of species range.Beyond advanced genetics, Drosophila melanogaster embryos provide additional advantages for studies at the cellular and molecular level, because behavioral responses to temperature change do not yet occur during the immotile early stages. Our characterization of temperature effects on early D. melanogaster development has revealed a unique temperature sensitivity of posttranslational modification of nucleocytoplasmic proteins with O-linked GlcNAc (O-GlcNAc). O-GlcNAc modification is known to occur on thousands of proteins involve...

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“…Fly strains and behavioral assays UAS-oga RNAi, UAS-ogt RNAi, and UAS-ogt flies have been described (Sinclair et al 2009;Park et al 2011), and UAS-ogt flies were kindly provided by Barry M. Honda (Simon Fraser University, Canada). tub-gal80 ts flies were kindly provided by KwangMin Choe (Yonsei University, Korea).…”

Section: Methodsmentioning

confidence: 99%

“…Immune complexes were analyzed for O-GlcNAc modification using the HGAC-85 antibody (A) or RL2 antibody (B). glucopyranoso-[2,1-D]-D29-thiazoline) (Macauley et al 2005;Park et al 2011), which inhibits OGA activity (Fig. 1B, cf.…”

Section: Dper Is O-glcnacylated In Drosophila Cultured Cellsmentioning

confidence: 99%

A role for O-GlcNAcylation in setting circadian clock speed

Kim¹,

Jeong²,

Park³

et al. 2012

Genes Dev.

Self Cite

113

102

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Post-translational modifications of one or more central ''clock'' proteins, most notably time-of-day-dependent changes in phosphorylation, are critical for setting the pace of circadian (y24 h) clocks. In animals, PERIOD (PER) proteins are the key state variable regulating circadian clock speed and undergo daily changes in abundance and cytoplasmic-nuclear distribution that are partly driven by a complex phosphorylation program. Here, we identify O-GlcNAcylation (O-GlcNAc) as a critical post-translational modification in circadian regulation that also contributes to setting clock speed. Knockdown or overexpression of Drosophila O-GlcNAc transferase (ogt) in clock cells either shortens or lengthens circadian behavioral rhythms, respectively. The Drosophila PERIOD protein (dPER) is a direct target of OGT and undergoes daily changes in O-GlcNAcylation, a modification that is mainly observed during the first half of the night, when dPER is predominantly located in the cytoplasm. Intriguingly, the timing of when dPER translocates from the cytoplasm to the nucleus is advanced or delayed in flies, wherein ogt expression is reduced or increased, respectively. Our results suggest that O-GlcNAcylation of dPER contributes to setting the correct pace of the clock by delaying the timing of dPER nuclear entry. In addition, OGT stabilizes dPER, suggesting that O-GlcNAcylation has multiple roles in circadian timing systems.

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Protein O-GlcNAcylation regulates Drosophila growth through the insulin signaling pathway

Cited by 14 publications

References 28 publications

The Increase in O-Linked N-Acetylglucosamine Protein Modification Stimulates Chondrogenic Differentiation Both in Vitro and in Vivo

The Increase in O-Linked N-Acetylglucosamine Protein Modification Stimulates Chondrogenic Differentiation Both in Vitro and in Vivo

O- GlcNAc reports ambient temperature and confers heat resistance on ectotherm development

A role for O-GlcNAcylation in setting circadian clock speed

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