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Modulation of apoptosis by the widely distributed Bcl-2 homologue Bak
M C Kiefer1, M J Brauer, V C Powers
1LXR Biotechnology Inc., Richmond, California 94804, USA.
Abstract:
Members of the Bcl-2 family of proteins are characterized by their ability to modulate cell death. Bcl-2 and some of its homologues inhibit apoptosis, whereas other family members, such as Bax, will accelerate apoptosis under certain conditions. Here we describe the identification and characterization of a complementary DNA that encodes a previously unknown Bcl-2 homologue designated Bak. Like Bax, the bak gene product primarily enhances apoptotic cell death following an appropriate stimulus. Unlike Bax, however, Bak can inhibit cell death in an Epstein-Barr-virus-transformed cell line. The widespread tissue distribution of Bak messenger RNA, including those containing long-lived, terminally differentiated cell types, suggests that cell-death-inducing activity is broadly distributed, and that tissue-specific modulation of apoptosis is controlled primarily by regulation of molecules that inhibit apoptosis.
Insights
Researchers identified Bak, a novel Bcl-2 family protein that enhances apoptosis. Bak
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- The Bcl-2 protein family regulates programmed cell death (apoptosis).
- Some Bcl-2 proteins inhibit apoptosis, while others, like Bax, promote it.
Purpose of the Study:
- To identify and characterize a new Bcl-2 family member, designated Bak.
- To understand Bak's role in apoptosis regulation.
Main Methods:
- Complementary DNA (cDNA) identification and characterization.
- Analysis of Bak gene product function in cell death.
- Expression analysis of Bak messenger RNA (mRNA) in various tissues.
Main Results:
- A novel Bcl-2 homologue, Bak, was identified.
- Bak enhances apoptotic cell death, similar to Bax.
- Bak demonstrated the ability to inhibit cell death in an Epstein-Barr-virus-transformed cell line.
- Bak mRNA is widely distributed across tissues, including terminally differentiated cells.
Conclusions:
- Bak is a novel Bcl-2 family member that primarily enhances apoptosis.
- The broad distribution of Bak suggests cell-death-inducing activity is widespread.
- Tissue-specific apoptosis modulation is likely controlled by regulators of apoptosis inhibitors.