Protein Palmitoylation Regulates Neural Stem Cell Differentiation by Modulation of EID1 Activity.
The functional significance of palmitoylation in the switch between self-renewal and differentiation of neural stem cells (NSCs) is not well defined, and the underlying mechanisms of protein palmitoylation are not well understood. Here, mouse NSCs were used as a model system and cell behavior was monitored in the presence of the protein palmitoylation inhibitor 2-bromopalmitate (2BRO). Our data show that 2BRO impaired the differentiation of NSCs into both neurons and glia and impaired NSC cell cycle exit. Moreover, the results show that palmitoylation modified E1A-like inhibitor of differentiation one (EID1) and this modification regulated EID1 degradation and CREB-binding protein (CBP)/p300 histone acetyltransferase activity at the switch between self-renewal and differentiation of NSCs. Our results extended the cellular role of palmitoylation, suggesting that it acts as a regulator in the acetylation-dependent gene expression network, and established the epigenetic regulatory function of palmitoylation in the switch between maintenance of multipotency and differentiation in NSCs.
Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong Provincial Key Laboratory of Mental Disorders, Department of Histology and Embryology, Shandong University School of Medicine, No. 44, Wenhua Xi Road, Jinan, Shandong, 250012, People's Republic of China.|Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, No. 350, Shushan Hu Road, Hefei, Anhui, 230031, People's Republic of China.
Xueran
X
Chen
Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong Provincial Key Laboratory of Mental Disorders, Department of Histology and Embryology, Shandong University School of Medicine, No. 44, Wenhua Xi Road, Jinan, Shandong, 250012, People's Republic of China.
Zhaoxia
Z
Du
Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong Provincial Key Laboratory of Mental Disorders, Department of Histology and Embryology, Shandong University School of Medicine, No. 44, Wenhua Xi Road, Jinan, Shandong, 250012, People's Republic of China.
Xian
X
Li
Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong Provincial Key Laboratory of Mental Disorders, Department of Histology and Embryology, Shandong University School of Medicine, No. 44, Wenhua Xi Road, Jinan, Shandong, 250012, People's Republic of China.
Liyan
L
Wang
Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong Provincial Key Laboratory of Mental Disorders, Department of Histology and Embryology, Shandong University School of Medicine, No. 44, Wenhua Xi Road, Jinan, Shandong, 250012, People's Republic of China.
Fuwu
F
Wang
Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong Provincial Key Laboratory of Mental Disorders, Department of Histology and Embryology, Shandong University School of Medicine, No. 44, Wenhua Xi Road, Jinan, Shandong, 250012, People's Republic of China.
Wei
W
Shi
Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong Provincial Key Laboratory of Mental Disorders, Department of Histology and Embryology, Shandong University School of Medicine, No. 44, Wenhua Xi Road, Jinan, Shandong, 250012, People's Republic of China. aijunhao@sdu.edu.cn.
Aijun
A
Hao
D000107:Acetylation; D000217:Acyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D050882:CREB-Binding Protein / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D000066673:Cell Self Renewal / Q000187:drug effects / Q000235:genetics; D050881:E1A-Associated p300 Protein / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006657:Histones / Q000378:metabolism; D054878:Lipoylation; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D010168:Palmitates / Q000494:pharmacology; D059748:Proteolysis / Q000187:drug effects; D012097:Repressor Proteins / Q000737:chemistry / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
C000592215:EID1 protein, mouse; D006657:Histones; D009687:Nuclear Proteins; D010168:Palmitates; D012097:Repressor Proteins; C022776:2-bromopalmitate; D000217:Acyltransferases; D050882:CREB-Binding Protein; D050881:E1A-Associated p300 Protein; C494361:Ep300 protein, mouse
2-bromopalmitate; CBP/p300; EID1; Mouse NSCs; Palmitoylation