P&S Journal: Winter 1995, Vol.15, No.1
The Dean's Award for Excellence in Research is awarded annually to the graduating Ph.D. student judged by a faculty-student committee to be most outstanding in his/her research accomplishment. The recipient of the 1994 Dean's Award was Dr. Joshua L. Dunaief, a graduate student in the laboratory of Dr. Stephen Goff in the Department of Microbiology. For his thesis research, Dr. Dunaief studied the complex formed by the retinoblastoma protein (RB) and a transcription factor (BRG1) and the role of this complex in tumor suppressor activity.
Prior research with the retinoblastoma protein showed that the RB protein can bring about tumor suppression by binding and inhibiting the activity of transcription factors such as E2F that are involved in cell-cycle progression. Dr. Dunaief's thesis work presented an additional and complementary mode of action for RB. Binding of the RB protein to a different transcription factor, namely BRG1, enhances the activity of that factor to induce cell cycle arrest. This finding thereby generated a new model: RB protein may accomplish tumor suppression by inhibiting cell cycle progression or by inducing cell cycle arrest.
One prediction of this new model was that BRG1 has tumor suppressor activity. Two lines of evidence have provided support for this prediction. First, it was found that while most tissues and cell lines express high levels of BRG1, at least two human carcinoma cell lines have either decreased or non-detectable levels of BRG1 expression. BRG1 deficiency in these cells may have led to tumorigenesis. Second, Dr. Dunaief provided a direct demonstration of tumor suppressor activity by showing that for one of these BRG1 deficient cell lines transfection with functional BRG1 yielded slow- or non-dividing and more differentiated cells. The research presented in Dr. Dunaief's thesis demonstrates the important role an RB-BRG1 complex may play in the control of the cell cycle and differentiation and it suggests that a mutation in either gene could be a critical step in carcinogenesis.