Function of p53 in Regulation of TSC Mutant Cell Apoptosis
Abstract
TSC1 and TSC2 are tumor suppressor genes that are mutated in tuberous sclerosis complex (TSC). Mutation in either TSC1 or TSC2 results in a constitutively activation of mammalian target of rapamycin (mTOR) therefore promoting cell growth. mTOR activity is regulated by intracellular signals including growth factors and cellular energy level. Energy starvation such as glucose deprivation inhibits mTOR activity via the activation of TSC2. We have observed that TSC cells are very sensitive to cellular energy starvation. This is because TSC cells fail to stop growth even in the absence of glucose while normal cells will stop grow under glucose starvation. The energy starvation induced cell death is due to apoptosis. P53 is the most frequently mutated human tumor suppressor. It has been reported that p53 is stabilized by AMPK which is activated by energy starvation. The major goal of this proposal is to investigate the functional importance of p53 in energy starvation induced apoptosis in TSC tumor cells. We will test whether p53 phosphorylation and protein levels are accumulated in TSC tumor cells. Furthermore we will investigate the function of TSC1 and TSC2 in p53 regulation. Completion of this proposal will establish a functional relationship between TSC1/TSC2 and p53 tumor suppressors.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2007
- Accession Number
- ADA477953
Entities
People
- Hun-liang Guan
Organizations
- University of Michigan