Abstract
Contrary to cell cycle-associated cyclin-dependent kinases, CDK5 is best known for its regulation of signaling processes in regulating mammalian CNS development. Studies of CDK5 have focused on its phosphorylation, although the diversity of CDK5 functions in the brain suggests additional forms of regulation. Here we expanded on the functional roles of CDK5 glycosylation in neurons. We showed that CDK5 was dynamically modified with O-GlcNAc in response to neuronal activity and that glycosylation represses CDK5-dependent apoptosis by impairing its association with p53 pathway. Blocking glycosylation of CDK5 alters cellular function and increases neuronal apoptosis in the cell model of the ICH. Our findings demonstrated a new role for O-glycosylation in neuronal apoptosis and provided a mechanistic understanding of how glycosylation contributes to critical neuronal functions. Moreover, we identified a previously unknown mechanism for the regulation of activity-dependent gene expression, neural development, and apoptosis.
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Acknowledgments
This work was supported by the National Natural Science Foundation of China (Nos. 81371299, 31300902, 81471188), the Colleges and Universities in Natural Science Research Project of Jiangsu Province (13KJB310009), a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), Technology Innovation Programme of Jiangsu Province (No. CXLX13_876), and Technology Innovation Programme of Nantong University (Nos. YKC13075, YKC13086).
Author’s Contribution
Xiaojin Ning, Jianhong Shen, Yuteng Ji, Lili Xie, Hongmei Wang, Ning Liu, Xide Xu, and Chi Sun did the experiments; Tao Tao did the statistic work; Dongmei Zhang designed the experimental plans; and Aiguo Shen and Kaifu Ke wrote the manuscript.
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Xiaojin Ning and Tao Tao contributed equally to this work.
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10571_2016_391_MOESM1_ESM.tif
Figure S1. (A) Hemin treatment at different concentrations (25, 50, 75, 100, and 150 μM) reduced cellular viability in a dose-dependent manner at indicative time point (3, 6, and 12 h) compared to untreated cells (control) assayed by CCK-8. (B) Hemin treatment (75 μM) reduced cellular viability in a time-dependent manner compared to untreated cells assayed by CCK-8.Supplementary material 1 (TIFF 182 kb)
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Ning, X., Tao, T., Shen, J. et al. The O-GlcNAc Modification of CDK5 Involved in Neuronal Apoptosis Following In Vitro Intracerebral Hemorrhage. Cell Mol Neurobiol 37, 527–536 (2017). https://doi.org/10.1007/s10571-016-0391-y
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DOI: https://doi.org/10.1007/s10571-016-0391-y