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Diva/Boo is a negative regulator of cell death in human glioma cells
U Naumann1, S Weit, J Wischhusen
1Laboratory of Molecular Neuro-Oncology, Department of Neurology, University of Tübingen, School of Medicine, Hoppe-Seyler-Str. 3, D-72076 Tübingen, Germany.
Abstract:
Diva is a novel proapoptotic member of the Bcl-2 protein family which binds apoptosis activating factor-1 (APAF-1). Diva is identical with Boo which was identified as a novel antiapoptotic Bcl-2 family protein. Here, we report that Diva promotes the cell cycle exit of human glioma cells in response to serum deprivation and inhibits apoptosis of these cells induced by CD95 ligand or chemotherapeutic drugs. In glioma cells, Diva interferes with apoptotic signaling downstream of cytochrome c release, but upstream of caspase activation, consistent with an inhibitory effect on the mitochondrial amplification step involving the apoptosome and APAF-1.
Insights
Diva, a Bcl-2 family protein, promotes glioma cell cycle exit and inhibits apoptosis. It interferes with apoptotic signaling, impacting the apoptosome and apoptosis activating factor-1 (APAF-1) pathway.
Area of Science:
- Molecular Biology
- Cell Biology
- Oncology
Background:
- The Bcl-2 protein family regulates apoptosis.
- Diva/Boo is a Bcl-2 family member with conflicting reports on its apoptotic role.
- Glioma is a common type of brain tumor.
Purpose of the Study:
- To investigate the role of Diva in human glioma cells.
- To elucidate the mechanism of Diva's action in apoptosis.
- To determine Diva's effect on cell cycle regulation.
Main Methods:
- Cell culture of human glioma cells.
- Induction of apoptosis using CD95 ligand and chemotherapeutic drugs.
- Analysis of apoptotic signaling pathways, including cytochrome c release and caspase activation.
- Assessment of cell cycle progression.
Main Results:
- Diva promotes cell cycle exit in glioma cells under serum deprivation.
- Diva inhibits apoptosis induced by CD95 ligand and chemotherapy.
- Diva acts downstream of cytochrome c release but upstream of caspase activation.
- Diva interferes with the mitochondrial amplification step involving the apoptosome and apoptosis activating factor-1 (APAF-1).
Conclusions:
- Diva functions as a pro-survival protein in human glioma cells.
- Diva's anti-apoptotic activity is mediated by interference with the apoptosome formation.
- Diva plays a role in regulating cell fate decisions in glioma.