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Inhibition of transcriptional regulator Yin-Yang-1 by association with c-Myc
A Shrivastava1, S Saleque, G V Kalpana
1Department of Biochemistry and Molecular Biophysics, Columbia University College of Physicians and Surgeons, New York, NY 10032.
Abstract:
Yin-Yang-1 (YY1) regulates the transcription of many genes, including the oncogenes c-fos and c-myc. Depending on the context, YY1 acts as a transcriptional repressor, a transcriptional activator, or a transcriptional initiator. The yeast two-hybrid system was used to screen a human complementary DNA (cDNA) library for proteins that associate with YY1, and a c-myc cDNA was isolated. Affinity chromatography confirmed that YY1 associates with c-Myc but not with Max. In cotransfections, c-Myc inhibits both the repressor and the activator functions of YY1, which suggests that one way c-Myc acts is by modulating the activity of YY1.
Insights
Yin-Yang-1 (YY1) protein interactions were studied. Researchers found that c-Myc modulates YY1's transcriptional functions, suggesting a new mechanism for c-Myc
Area of Science:
- Molecular Biology
- Gene Regulation
- Oncogenesis
Background:
- Yin-Yang-1 (YY1) is a transcription factor regulating key genes like c-fos and c-myc.
- YY1 exhibits context-dependent roles as a repressor, activator, or initiator of transcription.
Purpose of the Study:
- To identify proteins that interact with Yin-Yang-1 (YY1).
- To investigate the functional relationship between YY1 and c-Myc in transcriptional regulation.
Main Methods:
- Yeast two-hybrid system screening of a human cDNA library.
- Affinity chromatography to confirm protein-protein interactions.
- Cotransfection assays to assess functional effects.
Main Results:
- A c-myc cDNA was isolated, indicating an association between YY1 and c-Myc.
- Affinity chromatography confirmed YY1 binds to c-Myc but not Max.
- Cotransfection experiments showed c-Myc inhibits both repressor and activator functions of YY1.
Conclusions:
- c-Myc directly interacts with YY1.
- c-Myc modulates YY1's transcriptional activity, suggesting a novel regulatory mechanism.
- This interaction may play a role in the oncogenic functions of c-Myc.