Regulation of apoptosis-related genes by nitric oxide in cancer.

Nitric oxide (NO) is a simple molecule with a complex and pleiotropic biological activity. NO or related species have been implicated in the regulation of many genes that participate in many diverse biological functions including programmed cell death or apoptosis. Apoptosis is a process that may potentially be disrupted in cancer cells conferring a survival advantage. In addition, malignant tumor cells can develop an intricate system of resistance to apoptotic stimuli. NO or related species have been shown to play a dual role in the regulation of apoptosis in malignant cells either promoting cell death or protecting cells from pro-apoptotic induction. However, the specific role of NO in the regulation of apoptosis/survival-related genes expression seems to tilt the balance toward the promotion of pro-apoptotic and the suppression of anti-apoptotic genes. Herein we have reviewed the most relevant aspects involving NO and/or reactive intermediates in the regulation of apoptosis-related genes--mainly--at the transcriptional level. We described the basic apoptotic molecules that potentially are affected by NO and how NO-mediated signaling gets transmitted to the transcriptional machinery that governs the expression of these genes. In addition, we discussed some of the fundamental functional consequences of the regulation of apoptosis-related genes by NO in cancer biology and its potential therapeutic implications.

Transcription regulator Yin-yang 1: from silence to cancer.

Yin Yang (YY) 1 represents the epitome of what is considered to be a "Swiss army knife" transcription factor and regulator. YY1 is a ubiquitous and multifunctional zinc-finger transcription factor member of the Polycomb group protein family, a group of homeobox gene receptors that can act as activators or repressors of transcriptional activity. Furthermore, YY1 can act as a redox sensor, adaptor molecule, and chromatin structure and function regulator. YYl's characteristic function as transcriptional activator and repressor relies on its C2H2 (x4) zinc-finger structural DNA-binding motifs tangled with 2 specific regulatory domains. This structural conformation will render the activity of YY1 susceptible to changes in cellular redox status. YY1 also has been shown to undergo chromatin remodeling via interactions with histone acetyl transferase and histone deacetylase complexes. Both groups modify histones, resulting in altered chromatin structure. Herein, we will discuss the multiple roles and mechanisms of YY1 in the regulation of gene expression, its genetic factor functions, epigenetic regulatory activity, and its role as a redox sensor in the context of malignant neoplastic diseases.