DEPARTMENT OF DEFENSE - CONGRESSIONALLY DIRECTED MEDICAL RESEARCH PROGRAMS

BIG1 as a Potential Guanine Nucleotide Exchange Factor for Rheb

Principal Investigator: GUAN, KUN-LIANG
Institution Receiving Award: MICHIGAN, UNIVERSITY OF
Program: TSCRP
Proposal Number: TS050067
Award Number: W81XWH-06-1-0046
Funding Mechanism: Concept Award
Partnering Awards:
Award Amount: $100,000.00


PUBLIC ABSTRACT

Tuberous sclerosis complex (TSC) is a genetic disease with a prevalence of 1/6,000 in the population. TSC disease is caused by mutation in either the TSC1 or TSC2 tumor suppressor. The tumor suppressor gene normally inhibits tumor growth. Mutation (loss) of tumor suppressor often increases tumor growth. The function of TSC1 and TSC2 has been demonstrated. They inhibit the function of the Rheb gene. Rheb activity is high in TSC tumor. Therefore, uncontrolled Rheb activation is a major consequence of mutation in TSC1 or TSC2. A major question in the TSC research is to determine how Rheb is regulated. Based on previous studies in other fields, it is believed that Rheb also has activators. The main goal of this project is to identify the Rheb activator. Identification of the Rheb activator may provide a valuable tool for TSC treatment. The current model predicts that Rheb is constitutively activated in TSC patients. Inhibition of Rheb should decrease TSC tumor growth. Therefore, the Rheb activator will be an attractive target for future drug development.