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Forum on Immunopathological Diseases and Therapeutics
SJR: 0.164 SNIP: 0.041 CiteScore™: 0.18

ISSN Print: 2151-8017
ISSN Online: 2151-8025

Archives: Volume 1, 2010 to Volume 7, 2016

Forum on Immunopathological Diseases and Therapeutics

DOI: 10.1615/ForumImmunDisTher.v1.i1-2.30
pages 31-50

YY1 PcG function as a Potential cancer Therapeutic Target

Arindam Basu
University of Pennsylvania, School of Veterinary Medicine, Department of Animal Biology, Philadelphia, Pennsylvania, USA
Suchita Hodawadekar
University of Pennsylvania, School of Veterinary Medicine, Department of Animal Biology, Philadelphia, Pennsylvania, USA
Omozusi Andrews
University of Pennsylvania, School of Veterinary Medicine, Department of Animal Biology, Philadelphia, Pennsylvania, USA
Antionette Knox
University of Pennsylvania, School of Veterinary Medicine, Department of Animal Biology, Philadelphia, Pennsylvania, USA
Xuan Pan
University of Pennsylvania, School of Veterinary Medicine, Department of Animal Biology, Philadelphia, Pennsylvania, USA
Frank Wilkinson
Philadelphia University, School of Science and Health, Schoolhouse Lane and Henry Avenue, Philadelphia, Pennsylvania, USA
Michael L. Atchison
University of Pennsylvania, School of Veterinary Medicine, Department of Animal Biology, USA

ABSTRACT

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.