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Induction of apoptosis by the Bcl-2 homologue Bak
T Chittenden1, E A Harrington, R O'Connor
1Apoptosis Technology Inc., Cambridge, Massachusetts 02139, USA.
Abstract:
Cells are eliminated in a variety of physiological settings by apoptosis, a genetically encoded process of cellular suicide. Apoptosis comprises an intrinsic cellular defence against tumorigenesis, which, when suppressed, may contribute to the development of malignancies. The bcl-2 oncogene, which is activated in follicular lymphomas, functions as a potent suppressor of apoptosis under diverse conditions. Here we describe the complementary DNA cloning and functional analysis of a new Bcl-2 homologue, Bak, which promotes cell death and counteracts the protection from apoptosis provided by Bcl-2. Moreover, enforced expression of Bak induces rapid and extensive apoptosis of serum-deprived fibroblasts. This raises the possibility that Bak is directly involved in activating the cell death machinery.
Insights
Scientists discovered Bak, a new protein that promotes apoptosis (programmed cell death). Bak counteracts Bcl-2
Area of Science:
- Molecular Biology
- Cell Biology
- Oncology
Background:
- Apoptosis, or programmed cell death, is a critical cellular process.
- Suppression of apoptosis is linked to cancer development.
- The Bcl-2 oncogene inhibits apoptosis and is implicated in lymphomas.
Purpose of the Study:
- To clone and functionally analyze a novel Bcl-2 homologue, named Bak.
- To investigate Bak's role in apoptosis and its interaction with Bcl-2.
Main Methods:
- Complementary DNA (cDNA) cloning of the Bak gene.
- Functional analysis of Bak's role in promoting cell death.
- Enforced expression of Bak in fibroblasts.
Main Results:
- Bak was cloned and identified as a Bcl-2 homologue.
- Bak actively promotes apoptosis, counteracting Bcl-2's anti-apoptotic effects.
- Forced Bak expression led to rapid apoptosis in serum-deprived fibroblasts.
Conclusions:
- Bak is a novel protein that promotes programmed cell death.
- Bak may play a direct role in activating the cell death machinery.
- Bak represents a potential target for cancer therapies by inducing apoptosis.