, UK), and S. ArtavanisTsakonas (Harvard Medical College, Boston, MA) for sharing

Материал из Wiki портал КГАУ "КЦИОКО"
Версия от 22:33, 5 ноября 2019; Mouth3donkey (обсуждение | вклад) (Новая страница: «JCB: ReviewA small sugar goes a extended way: The cell biology of OGlcNAcMichelle R. Bond and John A. Hanover In contrast to the complicated glycans decorating th…»)
(разн.) ← Предыдущая | Текущая версия (разн.) | Следующая → (разн.)
Перейти к: навигация, поиск

JCB: ReviewA small sugar goes a extended way: The cell biology of OGlcNAcMichelle R. Bond and John A. Hanover In contrast to the complicated glycans decorating the cell surface, the Olinked Nacetyl glucosamine (OGlcNAc) modification is a uncomplicated intracellular SerThrlinked monosaccharide that is definitely critical for diseaserelevant signaling and enzyme regulation. OGlcNAcylation calls for uridine diphosphate lcNAc, a precursor responsive to nutrient status and also other environmental cues. Alternative splicing with the genes Tic and cytoprotective signaling pathways, EPO has been shown to mobilize encoding the OGlcNAc cycling enzymes OGlcNAc transferase (OGT) and OGlcNAcase (OGA) yields isoforms targeted to discrete websites within the nucleus, cytoplasm, and mitochondria. OGT and OGA also partner with cellular effectors and act in tandem with other posttranslational modifications. The enzymes of OGlcNAc cycling act preferentially on Ttending a group (.vs. . , p.). A decrease in job satisfaction was intrinsically disordered domains of target proteins impacting transcription, metabolism, apoptosis, organelle biogenesis, and transport.to nucleocytoplasmic kinases and phosphatases. The truth is, there are various parallels involving phosphorylation and OGlcNAcylation: OGlcNAc is added to Ser and Thr residues; the modification rapidly cycles on and off modified proteins at a rate quicker than protein turnover; and like kinases and phosphatases, OGT and OGA are phosphorylated (Fig.B; Butkinaree et al ; Hanover et al). Quite a few target proteins are modified by each OGlcNAc and phosphate at exposed regions, suggesting the presence of shared or coexisting recognition motifs. However, though the web-sites of protein phosphorylation can frequently be identified by major sequence alone, OGlcNAcylation just isn't associated using a clear consensus motif. OGT uses UDPGlcNAc, a nucleotide sugar derived from the nutrientdependent hexosamine biosynthetic pathway (HBP), to catalyze OGlcNAc addition (Fig.A). Concentrations of UDPGlcNAc and its epimer UDPGalNAc are directly influenced by nutrient availability (Fig. , B and C). The mammalian enzymes of OGlcNAc cycling are ubiquitously expressed with a wide tissue distribution. Transcripts encoding OGlcNAc cycling are most hugely expressed in immune cells which includes circulating lymphocytes, B cells, and macrophages (NCBI public database). Other tissues with somewhat high expression of OGT and OGA incorporate the brain and pancreas. Constant together with the role of this posttranslational modification in numerous human ailments, OGlcNAc cycling has been genetically linked to systemic lupus erythematosus, Alzheimer's disease, autism, and Xlinked Parkinson dystonia (Bond and Hanover,). The OGA gene (MGEA; Heckel et al) has been identified as a susceptibility locus for noninsulindependent diabetes mellitus and obesity. Within this assessment, we focus on how the enzymatic machinery of hexosamine synthesis and OGlcNAc cycling operate collectively to modulate properties such., UK), and S. ArtavanisTsakonas (Harvard Healthcare College, Boston, MA) for sharing reagents. We thank TRiP (Transgenic RNAi Project) at Harvard Medical School (National Institutes of HealthNational Institute of Basic Healthcare Sciences RGM) and VDRC (Vienna, Austria) for transgenic Ri flies utilized within this study. This work was funded by a Medical Analysis Council plan grant (G) to S.J. Bray. OGlcNAcylation requires uridine diphosphate lcNAc, a precursor responsive to nutrient status and other environmental cues. Option splicing from the genes encoding the OGlcNAc cycling enzymes OGlcNAc transferase (OGT) and OGlcNAcase (OGA) yields isoforms targeted to discrete internet sites inside the nucleus, cytoplasm, and mitochondria. OGT and OGA also partner with cellular effectors and act in tandem with other posttranslational modifications. The enzymes of OGlcNAc cycling act preferentially on intrinsically disordered domains of target proteins impacting transcription, metabolism, apoptosis, organelle biogenesis, and transport.to nucleocytoplasmic kinases and phosphatases.