Haltiwanger, R. S., Holt, G. D. & Hart, G. W. Enzymatic addition of O-GlcNAc to nuclear and cytoplasmic proteins. Identification of a uridine diphospho-N-acetylglucosamine:peptide β-N-acetylglucosaminyltransferase. J. Biol. Chem. 265, 2563–2568 (1990).

Article  CAS  PubMed  Google Scholar 

Hart, G. W., Housley, M. P. & Slawson, C. Cycling of O-linked β-N-acetylglucosamine on nucleocytoplasmic proteins. Nature 446, 1017–1022 (2007).

Article  CAS  PubMed  Google Scholar 

Yang, X. & Qian, K. Protein O-GlcNAcylation: emerging mechanisms and functions. Nat. Rev. Mol. Cell Biol. 18, 452–465 (2017).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lazarus, M. B., Nam, Y., Jiang, J., Sliz, P. & Walker, S. Structure of human O-GlcNAc transferase and its complex with a peptide substrate. Nature 469, 564–569 (2011).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Elsen, N. L. et al. Insights into activity and inhibition from the crystal structure of human O-GlcNAcase. Nat. Chem. Biol. 13, 613–615 (2017).

Article  CAS  PubMed  Google Scholar 

Bond, M. R. & Hanover, J. A. A little sugar goes a long way: the cell biology of O-GlcNAc. J. Cell Biol. 208, 869–880 (2015).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Nagel, A. K. & Ball, L. E. O-GlcNAc transferase and O-GlcNAcase: achieving target substrate specificity. Amino Acids 46, 2305–2316 (2014).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Stephen, H. M., Adams, T. M. & Wells, L. Regulating the regulators: mechanisms of substrate selection of the O-GlcNAc cycling enzymes OGT and OGA. Glycobiology 2021, 1–10 (2021).

Google Scholar 

Bullen, J. W. et al. Cross-talk between two essential nutrient-sensitive enzymes: O-GlcNAc transferase (OGT) and AMP-activated protein kinase (AMPK). J. Biol. Chem. 289, 10592–10606 (2014).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Harwood, K. R. & Hanover, J. A. Nutrient-driven O-GlcNAc cycling—think globally but act locally. J. Cell Sci. 127, 1857–1867 (2014).

CAS  PubMed  PubMed Central  Google Scholar 

Bond, M. R. & Hanover, J. A. O- GlcNAc cycling: a link between metabolism and chronic disease. Annu. Rev. Nutr. 33, 205–229 (2013).

Article  CAS  PubMed  PubMed Central  Google Scholar 

de Queiroz, R. M., Carvalho, E. & Dias, W. B. O-GlcNAcylation: the sweet side of the cancer. Front. Oncol. 4, 132 (2014).

Article  PubMed  PubMed Central  Google Scholar 

Qian, K. et al. Transcriptional regulation of O-GlcNAc homeostasis is disrupted in pancreatic cancer. J Biol. Chem. 293, 13989–14000 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ma, Z. & Vosseller, K. Cancer metabolism and elevated O-GlcNAc in oncogenic signaling. J. Biol. Chem. 289, 34457–34465 (2014).

Article  PubMed  PubMed Central  Google Scholar 

Sodi, V. L. et al. Signal transduction mTOR/MYC axis regulates O-GlcNAc transferase expression and O-GlcNAcylation in breast cancer. Mol. Cancer Res. 13, 923–933 (2015).

Martínez-Viturro, C. M. et al. Diazaspirononane nonsaccharide inhibitors of O-GlcNAcase (OGA) for the treatment of neurodegenerative disorders. J. Med. Chem. 63, 14017–14044 (2020).

Article  PubMed  Google Scholar 

Selnick, H. G. et al. Discovery of MK-8719, a potent O-GlcNAcase inhibitor as a potential treatment for tauopathies. J. Med. Chem. 62, 10062–10097 (2019).

Article  CAS  PubMed  Google Scholar 

Ryan, J. M. et al. O1-12-05: Phase 1 study in healthy volunteers of the O-Glcnacase inhibitor ASN120290 as a novel therapy for progressive supranuclear palsy and related tauopathies. Alzheimer’s Dement. 14, P251 (2018).

Article  Google Scholar 

Leney, A. C., El Atmioui, D., Wu, W., Ovaa, H. & Heck, A. J. R. Elucidating crosstalk mechanisms between phosphorylation and O-GlcNAcylation. Proc. Natl Acad. Sci. USA 114, E7255–E7261 (2017).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ruan, H. B., Nie, Y. & Yang, X. Regulation of protein degradation by O-GlcNAcylation: crosstalk with ubiquitination. Mol. Cell. Proteom. 12, 3489–3497 (2013).

Article  CAS  Google Scholar 

Ong, Q., Han, W. & Yang, X. O-GlcNAc as an integrator of signaling pathways. Front. Endocrinol. 9, 599 (2018).

Article  Google Scholar 

Tischer, D. & Weiner, O. D. Illuminating cell signalling with optogenetic tools. Nat. Rev. Mol. Cell Biol. 15, 551–558 (2014).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kwon, E. & Heo, W. D. Optogenetic tools for dissecting complex intracellular signaling pathways. Biochem. Biophys. Res. Commun. 527, 331–336 (2020).

Article  CAS  PubMed  Google Scholar 

Zhang, K. & Cui, B. Optogenetic control of intracellular signaling pathways. Trends Biotechnol. 33, 92–100 (2015).

Article  PubMed  Google Scholar 

Wu, Y. I. et al. A genetically encoded photoactivatable Rac controls the motility of living cells. Nature 461, 104–108 (2009).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kennedy, M. J. et al. Rapid blue-light-mediated induction of protein interactions in living cells. Nat. Methods 7, 973–975 (2010).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Toettcher, J. E., Voigt, C. A., Weiner, O. D. & Lim, W. A. The promise of optogenetics in cell biology: interrogating molecular circuits in space and time. Nat. Methods 8, 35–38 (2011).

Article  CAS  PubMed  Google Scholar 

Duan, L. et al. Optical activation of TrkA signaling. ACS Synth. Biol. 7, 1685–1693 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Huang, P. et al. Optical activation of TrkB signaling. J. Mol. Biol. 432, 3761–3770 (2020).

Article  CAS  PubMed  Google Scholar 

Zhang, K. et al. Light-mediated kinetic control reveals the temporal effect of the Raf/MEK/ERK pathway in PC12 cell neurite outgrowth. PLoS ONE 9, e92917 (2014).

Article  PubMed  PubMed Central  Google Scholar 

Toettcher, J. E., Weiner, O. D. & Lim, W. A. Using optogenetics to interrogate the dynamic control of signal transmission by the Ras/Erk module. Cell 155, 1422–1434 (2013).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ong, Q. et al. The timing of Raf/ERK and AKT activation in protecting PC12 cells against oxidative stress. PLoS ONE 11, e0153487 (2016).

Article  PubMed  PubMed Central  Google Scholar 

Paonessa, F. et al. Regulation of neural gene transcription by optogenetic inhibition of the RE1-silencing transcription factor. Proc. Natl Acad. Sci. USA 113, E91–E100 (2016).