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-kappaB) 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.