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	The association of GSK3 beta with E2F1 facilitates nerve growth factor-induced neural cell differentiation
	Zhou, Fangfang ; Zhang, Long ; Wang, Aijun ; Song, Bo ; Gong, Kai ; Zhang, Lihai ; Hu, Min ; Zhang, Xiufang ; Zhao, Nanming ; Gong, Yandao
	2010-05-11 ; 2010-05-11
关键词	SYNTHASE KINASE 3-BETA UBIQUITIN-PROTEASOME PATHWAY SUBCELLULAR-LOCALIZATION CYCLIN D1 NUCLEAR ACCUMULATION GENE-EXPRESSION AXON GROWTH DNA-DAMAGE PC12 CELLS DEGRADATION Biochemistry & Molecular Biology
中文摘要	It is widely acknowledged that E2F1 and GSK3 beta are both involved in the process of cell differentiation. However, the relationship between E2F1 and GSK3 beta in cell differentiation has yet to be discovered. Here, we provide evidence that in the differentiation of PC12 cells induced by nerve growth factor (NGF), GSK3 beta was increased at both the mRNA and protein levels, whereas E2F1 at these two levels was decreased. Both wild-type GSK3 beta and its kinase-defective mutant GSK3 beta KM can inhibit E2F1 by promoting its ubiquitination through physical interaction. In addition, the colocalization of GSK3 beta and E2F1 and their subcellular distribution, regulated by NGF, were observed in the process of PC12 differentiation. At the tissue level, GSK3 beta colocalized and interacted with E2F1 in mouse hippocampus. Furthermore, GSK3 beta facilitated neurite outgrowth by rescuing the promoter activities of Cdk inhibitors p21 and p15 from the inhibition caused by E2F1. To summarize, our findings suggest that GSK3 beta can promote the ubiquitination of E2F1 via physical interaction and thus inhibit its transcription activity in a kinase activity independent manner, which plays an important role in the NGF-induced PC12 differentiation.
语种	英语 ; 英语
出版者	AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC ; BETHESDA ; 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
内容类型	期刊论文
源URL	[http://hdl.handle.net/123456789/26872]
专题	清华大学
推荐引用方式 GB/T 7714	Zhou, Fangfang,Zhang, Long,Wang, Aijun,et al. The association of GSK3 beta with E2F1 facilitates nerve growth factor-induced neural cell differentiation[J],2010, 2010.
APA	Zhou, Fangfang.,Zhang, Long.,Wang, Aijun.,Song, Bo.,Gong, Kai.,...&Gong, Yandao.(2010).The association of GSK3 beta with E2F1 facilitates nerve growth factor-induced neural cell differentiation..
MLA	Zhou, Fangfang,et al."The association of GSK3 beta with E2F1 facilitates nerve growth factor-induced neural cell differentiation".(2010).

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