Polycomb Group (PcG) proteins are overexpressed in a variety of cancers including hematopoietic malignancies, prostate cancer, and breast cancer, as well as others. PcG proteins are involved in stem cell self-renewal and can prevent stem cell exhaustion. Therapeutic targeting of PcG protein function, therefore, may have a positive impact on treatment of cancers caused by PcG dysfunction. For instance, the transcriptional silencing pathway used by PcG protein EZH2 is mechanistically linked with highly malignant behavior of prostate cancer, and reducing EZH2 levels through RNAi approaches reduces prostate cancer cell proliferation. In addition, pharmacologic disruption of PcG function can induce apoptosis of cancer cells. Targeting the mechanism of PcG recruitment to DNA would be an attractive avenue for therapy. We previously showed that transcription factor YY1 is a PcG protein that can recruit PcG proteins to DNA, leading to transcriptional repression. We identified the REPO domain, a small 25-amino-acid domain of YY1 that is necessary and sufficient for YY1 PcG function and for DNA recruitment of PcG proteins. Here we show that a synthetic peptide encoding the REPO domain can inhibit growth of both prostate cancer and Abelson-transformed pro-B cell lines. This inhibition is rapid and results in induction of cell death. Therefore, molecules that inhibit YY1 PcG function may be therapeutically useful.
|Original language||English (US)|
|Number of pages||20|
|Journal||Forum on Immunopathological Diseases and Therapeutics|
|State||Published - Dec 1 2010|
All Science Journal Classification (ASJC) codes
- Molecular Medicine