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Transcription factor YY1: structure, function, and therapeutic implications in cancer biology

Oncogene volume 25, pages 1125–1142 (2006)Cite this article

Abstract

The ubiquitous transcription factor Yin Yang 1 (YY1) is known to have a fundamental role in normal biologic processes such as embryogenesis, differentiation, replication, and cellular proliferation. YY1 exerts its effects on genes involved in these processes via its ability to initiate, activate, or repress transcription depending upon the context in which it binds. Mechanisms of action include direct activation or repression, indirect activation or repression via cofactor recruitment, or activation or repression by disruption of binding sites or conformational DNA changes. YY1 activity is regulated by transcription factors and cytoplasmic proteins that have been shown to abrogate or completely inhibit YY1-mediated activation or repression; however, these mechanisms have not yet been fully elucidated. Since expression and function of YY1 are known to be intimately associated with progression through phases of the cell cycle, the physiologic significance of YY1 activity has recently been applied to models of tumor biology. The majority of the data are consistent with the hypothesis that YY1 overexpression and/or activation is associated with unchecked cellular proliferation, resistance to apoptotic stimuli, tumorigenesis and metastatic potential. Studies involving hematopoetic tumors, epithelial-based tumors, endocrine organ malignancies, hepatocellular carcinoma, and retinoblastoma support this hypothesis. Molecular mechanisms that have been investigated include YY1-mediated downregulation of p53 activity, interference with poly-ADP-ribose polymerase, alteration in c-myc and nuclear factor-kappa B (NF-κB) expression, regulation of death genes and gene products, and differential YY1 binding in the presence of inflammatory mediators. Further, recent findings implicate YY1 in the regulation of tumor cell resistance to chemotherapeutics and immune-mediated apoptotic stimuli. Taken together, these findings provide strong support of the hypothesis that YY1, in addition to its regulatory roles in normal biologic processes, may possess the potential to act as an initiator of tumorigenesis and may thus serve as both a diagnostic and prognostic tumor marker; furthermore, it may provide an effective target for antitumor chemotherapy and/or immunotherapy.

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Acknowledgements

We acknowledge the DOD/US Army Prostate Cancer Research Program DAMD170210023, The JCCF and Rosenfield Fund, and the Institutional Training Grant K12RR017611 (SG). We also acknowledge the assistance of Christine Yue, Pearl Chan, Samuel Olson and Todd Hutcherson in the preparation of this manuscript.

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Authors and Affiliations

  1. Department of Surgery Division of Transplantation, Dumont-UCLA Transplant Center, University of California, Los Angeles, CA, USA

    S Gordon

  2. Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA, USA

    S Gordon, G Akopyan & B Bonavida

  3. Department of Surgery, Division of Surgical Oncology, University of California, Los Angeles, CA, USA

    H Garban

  4. Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, University of California, Los Angeles, CA, USA

    H Garban & B Bonavida

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Correspondence to B Bonavida.

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Gordon, S., Akopyan, G., Garban, H. et al. Transcription factor YY1: structure, function, and therapeutic implications in cancer biology. Oncogene 25, 1125–1142 (2006). https://doi.org/10.1038/sj.onc.1209080

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