Diva/BclB regulates differentiation by inhibiting NDPKB/Nm23H2-mediated neuronal differentiation in PC-12 cells

BMC Neuroscience

Research Article

Jasmin Qian Ru Lim¹  Bei Ping He¹  Jia Lu² 

[1] Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, 117597, Singapore;Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, 117597, Singapore;DSO National Laboratories (DMERI@DSO), Defence Medical and Environmental Research Institute, 27 Medical Drive, 117510, Singapore, Singapore;

关键词: Diva/BclB;    NDPKB/Nm23H2;    Differentiation;    Neuritogenesis;    Proliferation;   

DOI  :  10.1186/1471-2202-13-123

 received in 2012-04-04, accepted in 2012-09-28,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundDiva (d eath i nducer binding to v Bcl-2 and A paf-1)/BclB is a Bcl-2 family member, which is known for its function in apoptosis. Diva/BclB has been shown to interact with NDPKB/Nm23H2, which is involved in cellular differentiation. Thus far, there has been no direct evidence of Diva/BclB having a role in differentiation. In the present study, we investigated the expression of Diva/BclB and NDPKB/Nm23H2 during differentiation in PC-12 cell line.ResultsOur results show that after differentiation, Diva/BclB expression was decreased and reciprocally, NDPKB/Nm23H2 expression was increased and it translocated into the nucleus. Overexpression of NDPKB/Nm23H2 promoted PC-12 neuronal differentiation by increasing neurite outgrowth and arresting cell cycle progression. There was a concurrent downregulation of Diva/Boo when NDPKB/Nm23H2 was overexpressed, which mirrors the effect of NGF on PC-12 cell differentiation. Overexpression of Diva/BclB did not change the expression level of NDPKB/Nm23H2, but inhibited its nuclear localization. Cells that overexpressed Diva/BclB presented a decreased percentage of differentiated cells and average neurite length was shortened. This was due to an increase in the formation of Diva/BclB and NDPKB/Nm23H2 complexes as well as Diva/BclB and β-tubulin complexes. Concomitantly, there was a decrease in formation of NDPKB/Nm23H2 and β-tubulin complexes. Overexpression of Diva/BclB also resulted in a higher percentage of S-phase cells.ConclusionOur results showed a novel role for Diva/BclB in neuronal differentiation. Its downregulation during neuronal differentiation may be necessary to allow NDPKB/Nm23H2 and β-tubulin interaction that promotes NDPKB/Nm23H2 mediated differentiation.

【 授权许可】

Unknown   
© Lim et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.