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Updated: Jul 31, 2026
08:18
Focus Formation: A Cell-based Assay to Determine the Oncogenic Potential of a Gene
Published on: December 31, 2014
Transcriptional control by myb oncogene product
S Ishii1, T Nomura, C Kanei-Ishii
1Laboratory of Molecular Genetics, Tsukuba Life Science Center, Ibaraki, Japan.
The Tohoku Journal of Experimental Medicine
|October 1, 1992
Summary
Disrupting the leucine zipper in c-Myb
Area of Science:
- Molecular Biology
- Protein Structure and Function
- Oncogenesis
Background:
- The c-Myb protein is a transcription factor involved in cell proliferation and differentiation.
- Dysregulation of c-Myb is implicated in various cancers.
- Understanding the structural and functional domains of c-Myb is crucial for deciphering its role in oncogenesis.
Purpose of the Study:
- To analyze the structure and function of two key domains of the c-Myb protein.
- To investigate the role of the leucine zipper in the negative regulatory domain of c-Myb.
- To elucidate the structural model of the Myb DNA-binding domain.
Main Methods:
- Biochemical analysis of protein domains.
- Site-directed mutagenesis to disrupt the leucine zipper structure.
- Nuclear Magnetic Resonance (NMR) spectroscopy to analyze the DNA-binding domain structure.
Main Results:
- Disruption of the leucine zipper significantly enhanced the transactivating and transforming capacities of c-Myb.
- Evidence suggests an inhibitor binds c-Myb via the leucine zipper, suppressing transactivation.
- A "tryptophan cluster" model for the Myb DNA-binding domain was proposed, with NMR confirming the role of conserved tryptophans in the hydrophobic core.
- Oncogenic activation of c-Myb by missense mutation is suggested.
Conclusions:
- The leucine zipper is a critical component of the negative regulatory domain of c-Myb.
- Modulation of the leucine zipper interaction offers a potential therapeutic strategy for c-Myb-driven cancers.
- The "tryptophan cluster" model provides new insights into the structural integrity and function of the Myb DNA-binding domain.
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