Diva/BclB regulates differentiation by inhibiting NDPKB/Nm23H2-mediated neuronal differentiation in PC-12 cells.
BMC Neurosci
; 13: 123, 2012 Oct 11.
Article
em En
| MEDLINE
| ID: mdl-23057762
ABSTRACT
BACKGROUND:
Diva (death inducer binding to vBcl-2 and Apaf-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 ß-tubulin complexes. Concomitantly, there was a decrease in formation of NDPKB/Nm23H2 and ß-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 ß-tubulin interaction that promotes NDPKB/Nm23H2 mediated differentiation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Diferenciação Celular
/
Núcleosídeo-Difosfato Quinase
/
Proteínas Proto-Oncogênicas c-bcl-2
/
Nucleosídeo NM23 Difosfato Quinases
/
Neurônios
Limite:
Animals
Idioma:
En
Revista:
BMC Neurosci
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Singapura