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Research Description:
My lab is interested in the transcriptional control of cellular proliferation and how these controls are subverted in human malignancy. Our efforts are focused on understanding the function of the Max network of transcription factors and how the mSin3A/HDAC corepressor complex drives transcriptional repression.
The Max network of transcription factors is a key regulator of cell proliferation, differentiation and death. The Myc protein is a transcriptional activator and constitutes a positive branch of the Max network. Alteration in Myc levels or activity is associated with approximately 70,000 cancer deaths annually in the United States alone. Currently, we are examining the function of the Mondo family of Myc-like transcription factors. In contrast to Myc, Mad functions as a transcriptional repressor, blocks Myc function and comprises a negative branch of the Max network. Mad functions as a transcriptional repressor by interacting with the mSin3A corepressor. mSin3A is a component of a large multiprotein complex that uses the enzymatic activity of associated histone deacetylases to repress transcription. We have purified this large corepressor complex and have isolated cDNAs encoding each mSin3A-associated protein. We are now determining the contribution of each of these proteins to the function of this important corepressor.
Research Keywords:
Nuclear oncogenes, Transcription repression, Histone deacetylase, bHLHZip family