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

BMC Neuroscience

Bei Ping He²  Jia Lu¹  Jasmin Qian Ru Lim² 

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

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

Others  :  1140866
DOI  :  10.1186/1471-2202-13-123

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

【 摘 要 】

Background

Diva

(

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.

Results

Our 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.

Conclusion

Our 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】

   
2012 Lim et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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