The association of GSK3β with E2F1 facilitates nerve growth factor-induced neural cell differentiation

Fangfang Zhou, Long Zhang, Aijun Wang, Bo Song, Kai Gong, Lihai Zhang, Min Hu, Xiufang Zhang, Nanming Zhao, Yandao Gong

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

It is widely acknowledged that E2F1 and GSK3β are both involved in the process of cell differentiation. However, the relationship between E2F1 and GSK3β 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), GSK3β was increased at both the mRNA and protein levels, whereas E2F1 at these two levels was decreased. Both wild-type GSK3β and its kinase-defective mutant GSK3β KM can inhibit E2F1 by promoting its ubiquitination through physical interaction. In addition, the colocalization of GSK3β and E2F1 and their subcellular distribution, regulated by NGF, were observed in the process of PC12 differentiation. At the tissue level, GSK3β colocalized and interacted with E2F1 in mouse hippocampus. Furthermore, GSK3β 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 GSK3β 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.

Original languageEnglish (US)
Pages (from-to)14506-14515
Number of pages10
JournalJournal of Biological Chemistry
Volume283
Issue number21
DOIs
StatePublished - May 23 2008
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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    Zhou, F., Zhang, L., Wang, A., Song, B., Gong, K., Zhang, L., Hu, M., Zhang, X., Zhao, N., & Gong, Y. (2008). The association of GSK3β with E2F1 facilitates nerve growth factor-induced neural cell differentiation. Journal of Biological Chemistry, 283(21), 14506-14515. https://doi.org/10.1074/jbc.M706136200