New Orleans, LA Michael Lan, PhD, Professor of Pediatrics and Genetics at LSU Health Sciences Center New Orleans, is the senior author of a paper revealing the molecular mechanism of how a protein determines the fate of the cells that make and release insulin. Zinc Finger Transcription Factor INSM1 Interrupts Cyclin D1 and CDK4 Binding and Induces Cell Cycle Arrest, a paper in press currently available online, will be published in the Journal of Biological Chemistry, Vol. 284, Issue 9, 5574-5581, February 27, 2009.
Dr. Lan's laboratory is studying INSM1, a protein involved in the regulation of hormone- producing, or endocrine, cells. INSM1 plays a critically important role in the development of pancreatic beta cells the only cells in the body that secrete insulin. Beta cells are located in islet cell clusters throughout the pancreas. Diabetes mellitus type 1 results from the destruction or dysfunction of islets and their beta cells. Type 2 diabetes results from the body's inability to use insulin properly and a gradual decrease in the pancreas's ability to make it.
In this study, the research group used pancreatic cancer cells to investigate the effects of INSM1 on cell cycle function. INSM1 is a transcription factor a protein that binds to specific sequences of DNA and controls the target gene expression or action. The researchers developed an inducible system to "turn on" INSM1 in pancreatic cancer cells and found that it resulted in a significant reduction in the cells' growth rate. They showed that the mechanism for this growth inhibition was due to an interaction between INSM1 and cyclin D1, an important cell growth promoting protein. Through the interaction between these two proteins, the growth of the tumor cells was impaired. Further, transplantation of these INSM1 on pancreatic tumor cells into mice showed the growth rate of these tumor cells was significantly inhibited compared to the control cells.
"Taken together, we provide evidence to support that INSM1 binds to cyclin D1, a critical factor in cell growth, and interrupts normal cellular proliferation," notes Dr. Lan. "Our study furthers our understanding of how to control islet cell growth in the culture system, which may ultimately benefit diabetes."
|Contact: Leslie Capo|
Louisiana State University Health Sciences Center