Email updates

Keep up to date with the latest news and content from BMC Neuroscience and BioMed Central.

Open Access Research article

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

Jasmin Qian Ru Lim1, Jia Lu12 and Bei Ping He1*

Author affiliations

1 Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, 117597, Singapore

2 Defence Medical and Environmental Research Institute, DSO National Laboratories (DMERI@DSO), 27 Medical Drive, Singapore, 117510, Singapore

For all author emails, please log on.

Citation and License

BMC Neuroscience 2012, 13:123  doi:10.1186/1471-2202-13-123

Published: 11 October 2012




nducer binding to
Bcl-2 and
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.


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.


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.

Diva/BclB; NDPKB/Nm23H2; Differentiation; Neuritogenesis; Proliferation