Related Experiment Videos
A dominant interfering Myb mutant causes apoptosis in T cells
D Taylor1, P Badiani, K Weston
1CRC Centre for Cell and Molecular Biology, Institute of Cancer Research, London, UK.
Genes & Development
|November 1, 1996
Summary
The c-Myb transcription factor regulates cell survival in blood cell production. This study reveals c-Myb directly controls the bcl-2 gene, impacting apoptosis during hematopoiesis.
Area of Science:
- Molecular Biology
- Cell Biology
- Hematopoiesis
Background:
- The c-Myb transcription factor is crucial for hematopoietic lineage development.
- Its precise mechanisms of action and regulated genes remain incompletely understood.
Purpose of the Study:
- To investigate the role of c-Myb in regulating cell survival during hematopoiesis.
- To identify key genes directly targeted by c-Myb.
Main Methods:
- Development of an inducible dominant interfering Myb protein (c-Myb DNA binding domain, Engrailed repressor domain, modified estrogen receptor).
- Expression of the mutant protein in murine EL4 thymoma cells and transgenic mice.
- Assays included apoptosis assessment, cell-cycle analysis, bcl-2 expression studies, and promoter analysis (run-on transcription, bandshifting, transient expression).
Main Results:
- Induction of the dominant interfering Myb mutant triggered apoptosis in EL4 cells and thymocytes without affecting cell-cycle progression.
- Apoptosis correlated with down-regulation of bcl-2, but not other bcl-2 family members.
- Overexpression of bcl-2 rescued thymocytes from Myb-induced death.
- bcl-2 was identified as a direct transcriptional target of c-Myb.
Conclusions:
- c-Myb plays a critical role in regulating cell survival during hematopoiesis.
- The bcl-2 gene is a direct target of c-Myb, mediating its effects on cell survival.
- These findings establish a novel function for Myb proteins in controlling apoptosis within hematopoietic lineages.