Disrupting the enzyme complex regulating O-GlcNAcylation blocks signaling and development

Whisenhunt, Thomas R.; Yang, Xiaoyong; Bowe, Damon B.; Paterson, Andrew J.; Tine, Brian A. Van; Kudlow, Jeffrey E.

doi:10.1093/glycob/cwj096

Cited by 104 publications

(125 citation statements)

References 45 publications

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“…Recently, Whisenhunt et al 31 showed by in vitro experiments that OGT forms a Among the HRT-responding genes we also found genes encoding both catabolic and anabolic agents. Androgen receptor (Ar) was significantly upregulated (13 %) in the HRT group.…”

supporting

confidence: 58%

Muscular Transcriptome in Postmenopausal Women With or Without Hormone Replacement

Pöllänen

Ronkainen

Suominen

et al. 2007

Rejuvenation Research

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The loss of muscle mass and strength with aging is well characterized, but our knowledge of the molecular mechanisms underlying the development of sarcopenia remains incomplete. Although menopause is often accompanied with first signs of age-associated changes in muscle structure and function, the effects of hormone replacement therapy (HRT) or menopause-related decline in estrogen production in the muscles of postmenopausal women is not well understood.Furthermore the knowledge of the global transcriptional changes that take place in skeletal muscle in relation to estrogen status has thus far been completely lacking. We used a randomized double-blinded study design together with an explorative microarray experiment to characterize possible effects of continuous, combined HRT and estrogen deprivation on the skeletal muscle of fifteen women. Here, we report the differential response of both GO-annotated biological processes and some individual genes responding differentially to the use or non-use of HRT. Our results revealed transcription level changes in, e.g., muscle protein and energy metabolism. In particular, the ubiquitine-proteosome system was found to be effected at several levels. HRT seemed to partially counteract the postmenopause-related transcriptional changes. Our results suggest that during the early postmenopausal years, when there is no counteracting medication available, muscle transcriptome changes notably, whereas HRT appears to slow-down this phenomenon and could therefore aid in maintaining proper muscle mass and function after menopause.3

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supporting

confidence: 58%

Muscular Transcriptome in Postmenopausal Women With or Without Hormone Replacement

Pöllänen

Ronkainen

Suominen

et al. 2007

Rejuvenation Research

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“…The decrease in fertility is closely correlated to glucose concentration, suggesting that OGT-1 is acting as a nutrient sensor. O-GlcNAc cycling has also been implicated in the response to starvation, as OGT expression increases and OGA expression decreases in response to glucose deprivation (Kreppel et al 1997;Whisenhunt et al 2006), indicating that this pathway is finely tuned to maintain homeostasis.…”

Section: Discussionmentioning

confidence: 99%

O-Linked-N-Acetylglucosamine Cycling and Insulin Signaling Are Required for the Glucose Stress Response inCaenorhabditis elegans

et al. 2011

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In a variety of organisms, including worms, flies, and mammals, glucose homeostasis is maintained by insulin-like signaling in a robust network of opposing and complementary signaling pathways. The hexosamine signaling pathway, terminating in O-linked-N-acetylglucosamine (O-GlcNAc) cycling, is a key sensor of nutrient status and has been genetically linked to the regulation of insulin signaling in Caenorhabditis elegans. Here we demonstrate that O-GlcNAc cycling and insulin signaling are both essential components of the C. elegans response to glucose stress. A number of insulin-dependent processes were found to be sensitive to glucose stress, including fertility, reproductive timing, and dauer formation, yet each of these differed in their threshold of sensitivity to glucose excess. Our findings suggest that O-GlcNAc cycling and insulin signaling are both required for a robust and adaptable response to glucose stress, but these two pathways show complex and interdependent roles in the maintenance of glucose-insulin homeostasis.

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“…Using high stringency reporter selection, we were able to identify 27 putative binding partners for OGT (Table 1). In our screen, two previously known interacting partners for OGT were successfully identified, namely O-GlcNAcase (25) and Trak1 (previously known as OIP106) (15). It is interesting to note that the proteins identified belong to a wide range of functional classes from ion transporting integral membrane proteins to signaling and transcriptional regulators.…”

Section: Putative Ogt-interacting Proteins Were Identified Using Amentioning

confidence: 94%

O-Linked β-N-Acetylglucosaminyltransferase Substrate Specificity Is Regulated by Myosin Phosphatase Targeting and Other Interacting Proteins

Cheung¹,

Sakabe²,

Housley

et al. 2008

Journal of Biological Chemistry

149

153

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O-GlcNAc-transferase (OGT) substrate specificity is regulated by transiently interacting proteins. To further examine the regulation of OGT, we have identified 27 putative OGT-interacting proteins through a yeast two-hybrid screen. Two of these proteins, Trak1 (OIP106) and O-GlcNAcase, have been shown previously to interact with and regulate OGT. We demonstrate here that MYPT1 and CARM1 also interact with and target OGT. MYPT1 and CARM1 are substrates of OGT in vitro and in vivo. MYPT1 and CARM1 also function to alter OGT substrate specificity in vitro. Furthermore depletion of MYPT1 in Neuro-2a neuroblastoma cells alters GlcNAcylation of several proteins under basal conditions, suggesting that MYPT1 regulates OGT substrate specificity in vivo.

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Disrupting the enzyme complex regulating O-GlcNAcylation blocks signaling and development

Cited by 104 publications

References 45 publications

Muscular Transcriptome in Postmenopausal Women With or Without Hormone Replacement

Muscular Transcriptome in Postmenopausal Women With or Without Hormone Replacement

O-Linked-N-Acetylglucosamine Cycling and Insulin Signaling Are Required for the Glucose Stress Response inCaenorhabditis elegans

O-Linked β-N-Acetylglucosaminyltransferase Substrate Specificity Is Regulated by Myosin Phosphatase Targeting and Other Interacting Proteins

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