The O-GlcNAc Modification of CDK5 Involved in Neuronal Apoptosis Following In Vitro Intracerebral Hemorrhage.
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.
Department of Neurology, Affiliated Hospital of Nantong University, Nantong, 226001, China.|Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226001, China.
Xiaojin
X
Ning
Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226001, China.
Tao
T
Tao
Department of Neurosurgery, Affiliated Hospital of Nantong University, Nantong, 226001, China.
Jianhong
J
Shen
Department of Neurology, Affiliated Hospital of Nantong University, Nantong, 226001, China.|Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226001, China.
Yuteng
Y
Ji
Department of Neurology, Affiliated Hospital of Nantong University, Nantong, 226001, China.|Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226001, China.
Lili
L
Xie
Department of Neurology, Affiliated Hospital of Nantong University, Nantong, 226001, China.|Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226001, China.
Hongmei
H
Wang
Department of Neurology, Affiliated Hospital of Nantong University, Nantong, 226001, China.|Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226001, China.
Ning
N
Liu
Department of Neurosurgery, Affiliated Hospital of Nantong University, Nantong, 226001, China.
Xide
X
Xu
Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226001, China.
Chi
C
Sun
Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226001, China.
Dongmei
D
Zhang
Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226001, China. shag@ntu.edu.cn.|Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, 226001, China. shag@ntu.edu.cn.
Aiguo
A
Shen
Department of Neurology, Affiliated Hospital of Nantong University, Nantong, 226001, China. kekaifu_nt@126.com.
Kaifu
K
Ke
D000117:Acetylglucosamine / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002543:Cerebral Hemorrhage / Q000201:enzymology* / Q000473:pathology*; D051360:Cyclin-Dependent Kinase 5 / Q000378:metabolism*; D006031:Glycosylation / Q000187:drug effects; D057809:HEK293 Cells; D006427:Hemin / Q000494:pharmacology; D006801:Humans; D008954:Models, Biological; D009474:Neurons / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology*; D016716:PC12 Cells; D051381:Rats
D006427:Hemin; D051360:Cyclin-Dependent Kinase 5; C495905:CDK5 protein, human; D000117:Acetylglucosamine
CDK5; Intracerebral hemorrhage; Neuronal apoptosis; O-GlcNAc modification