Hexosamine Signaling Pathway: O-GlcNAc cycling in feast or famine

As a modulator of signaling, endocytosis, transcription, translation and protein stability, the HSP may coordinately regulate nutrient sparing and salvage. Some of the key intracellular targets of O-GlcNAc modification are shown with respect to their role in nutrient uptake and salvage. OGT modifies numerous signaling cascades including those triggered by PI3K, MAPK, AMPK and mTOR (For details, see ). In addition, by interacting with adapters like the D. melanogaster protein Milton, OGT may modulate intracellular movement of mitochondria on microtubules. The mammalian Milton homolog GRIF-1 binds to OGT and may be involved in orchestrating directed organelle movement including the trafficking of neurosecretory vesicles, endosomes, lysosomes and autophagosomes. These processes are critical for nutrient acquisition and immunity. OGT overexpression alters the movement of GLUT4 rich endosomes to the plasma membrane in response to insulin, a hallmark of mammalian insulin resistance. O-GlcNAc may also play a role in the switch from anabolic to catabolic metabolism. For example, O-GlcNAc modifies many ribosomal proteins and is required for the formation of stress granules involved in mRNA triage. O-GlcNAc also regulates the proteasome by modifying the ATP-dependent rpt2 domain as described in the text, and may directly, or indirectly regulate autophagy. O-GlcNAc also modifies nuclear pores and transcription-complexes playing an essential role in transcriptional repression [].

Publication

The Hexosamine Signaling Pathway: O-GlcNAc cycling in feast or famine. () John A. Hanover, et al. Biochim Biophys Acta. ;1800(2):80. Figure: F6. All organisms Drosophila melanogaster Homo sapiens

Disease mentions