Understanding tuberous sclerosis

Tuberous sclerosis (TSC) is a prevalent inherited disease that is caused by mutations in either the TSC1 or TSC2 gene. By generating fruit flies deficient in TSC1, researchers from the University of Texas Southwestern Medical Center have been able to determine that TSC1 and TSC2 antagonize insulin signaling and thereby regulate cell growth.

TSC is characterized by the development of benign tumors throughout various bodily organs. Patients often display skin rashes, seizures and mental retardation as a result of these tumors. Although TSC affects 1 in 6000 live births, or 50,000 people in the United States and over one million people worldwide, until relatively recently the chain of biological events linking TSC gene mutation and tumorigenesis has remained unclear.

As published in Genes & Development, Dr. Duojia Pan and Dr. Xinsheng Gao have determined that TSC1 and TSC2 proteins form complexes in cells, and negatively regulate the insulin pathway in Drosophila. In Drosophila the insulin signaling pathway controls cellular growth and organ size through a multi-step enzymatic cascade. Drs. Gao and Pan found that TSC1 and TSC2 act in a parallel pathway, which converges upon the insulin pathway in such a way as to decrease the effect of insulin on promoting cell growth.

Drs. Gao and Pan found that fly cells deficient in TSC1 display increased cell size, as is also sometimes true in tumors derived from human TSC patients. Further delineation of the role of TSC1 and TSC2 in cell growth regulation will provide valuable insight into the mechanism of this disease and direct therapeutic strategies.


Contact: Nora Poppito
please e-mail
Cold Spring Harbor Laboratory

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