What makes Bright a proto-oncogene?


What makes Bright a proto-oncogene?

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Title: What makes Bright a proto-oncogene?
Author: Mathur, Shawn
Abstract: Cancer is now the second leading cause of death in the developed world and accounts for 1 out of every 4 deaths in the US (American Cancer Society). The fundamental defect of cancer is unregulated cell division. One way this can happen is from an increase in the activity of proteins which signal cell growth. These proteins, called proto-oncogenes, possess normal functions in cells but can induce unregulated cell division when permanently activated by mutation. Understanding the molecular biology behind proto-oncogenes may lead to insight into how cancer develops and aid in the development of better treatment options for cancer patients. We are interested in studying Bright, a proto-oncogene expressed in mouse B-cells, white blood cells which are an essential part of the immune system. Bright can induce proliferation when overexpressed in normal cells. Our ultimate goal is to understand the mechanism by which Bright causes cells to become cancer-like. Bright’s oncogenic activity is correlated with an increase in function of E2F1, a protein considered to be a master regulator of cell division. E2F1 controls the transcription of many genes needed to drive the cell cycle. Specifically, we are interested in understanding how Bright upregulates the ability of E2F1 to activate transcription of its target genes. Various lines of evidence suggest that Bright may disrupt the action of pRb/E2F1 complexes which normally repress E2F1 production at the E2F1 promoter. Several biological studies have been performed to investigate this possibility and to learn more about the action of Bright. In our first experiment, we determine which properties of Bright are necessary to transform cells. Second, we show that Bright can associate with pRb, suggesting that Bright may play a role in E2F1 regulation. Finally, chromatin immunoprecipitation assays suggest that Bright associates with the E2F1 promoter and may indeed affect the function of pRb/E2F1 repressive complexes. Thus, we provide evidence in support of a novel model for Bright’s oncogenic properties. Our findings are particularly relevant for patients with Activated B cell-like Diffuse Large B-cell Lymphoma, a highly pernicious cancer that appears to involve the human version of Bright. Further studies to explore the nature of Bright's interaction with the Rb/E2F1 protein complex may lead to a better prognosis for these patients.
Department: Biological Sciences, School of
Subject: College of Natural Sciences oncogenes cancer proto-oncogenes Bright E2F1 proteins
URI: http://hdl.handle.net/2152/13393
Date: 2009-05

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