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Myc represses the p21(WAF1/CIP1) promoter and interacts with Sp1/Sp3
1Department of Molecular Genetics, University of Illinois College of Medicine, Chicago, IL 60607, USA. agartel@uic.edu
Summary
The oncogene Myc suppresses the transcription of the cell cycle inhibitor p21(WAF1/CIP1) by interacting with Sp1. This mechanism may enable Myc to promote cancer cell proliferation.
Area of Science:
- Molecular Biology
- Cell Biology
- Oncology
Background:
- p21 (WAF1/CIP1) is a cyclin-dependent kinase inhibitor that halts cell proliferation and causes cell cycle arrest.
- The oncogene Myc can override this arrest, suggesting a role in cell proliferation and cancer.
Purpose of the Study:
- To investigate the molecular mechanism by which Myc represses p21 transcription.
- To determine if Myc's interaction with transcription factors mediates p21 repression.
Main Methods:
- Activation of a Myc-estrogen receptor fusion protein in mouse cells.
- Transient transfection assays with p21 promoter constructs.
- Coimmunoprecipitation and glutathione S-transferase pull-down assays to study protein interactions.
Main Results:
- Myc activation suppressed endogenous p21 transcription independently of protein synthesis or histone deacetylase activity.
- Myc repressed a minimal p21 promoter region containing Sp1-binding sites.
- c-Myc was found to interact with Sp1/Sp3, and specifically with the zinc finger domain of Sp1.
Conclusions:
- Myc likely down-regulates p21 transcription by sequestering the transcription factor Sp1, which is essential for p21 expression.
- This repression mechanism may contribute to Myc's role in promoting cell proliferation and potentially cancer development.