Mutra, R.; Vallabhapurapu, S.

NF-kappaB is primarily known for its transcriptional activation function in the context of immune responses, inflammation, cell survival, proliferation and Cancer. However, whether NF-kappaB functions as a transcriptional repressor in the context of tumor growth has not been well addressed. While, classical NF-kappaB activated by IKK-beta has been shown to play a tumor promoting role in colorectal cancer, couple of studies suggested that overexpression of RelA in colorectal cancer cells leads to apoptosis. These findings were contradictor and puzzling with regards to the role of RelA in colorectal cancer. Here, we report that RelA represses proapoptotic gene puma and contributes to colorectal cancer cell survival. Interestingly, Yin-Yang1, a RelA target gene product is also essential to repress puma and contributes to colorectal cancer cell survival. Moreover, RelA and YY1 form a complex in colorectal cancer cells. Depletion of either RelA or YY1 results in upregulation of pro-apoptotic gene Puma. Importantly, we show that binding of Yin Yang1 to RelA impairs transcriptional activation by RelA suggesting that YY1 is an inhibitor of RelA function. Collectively, we present evidence for RelA-YY1 complex formation in colorectal cancer cells, both RelA and YY1 function as transcriptional repressors of puma and contribute to survival of colorectal cancer cells.