Regulating Size

Abstract

The proteins TSC1 and TSC2 can be found in a complex, and mutations in the genes for these proteins are associated with the human disorder tuberous sclerosis (a condition characterized by benign tumors in multiple organs). Two groups (Tapon et al . and Potter et al .) identified and characterized the TSC1 and TSC2 homologs in Drosophila . The Drosophila Tsc1 gene was identified in screens for mosaic flies with enlarged eyes. The mutant cells were larger than the adjacent wild-type cells, and this phenotype could be observed in several tissues in addition to the eye. Disruption of either the Tsc1 or Tsc2 gene resulted in increased cell number and cell size in many organs, with an increase in the number of cells in the cell cycle and a decrease in the length of time spent in G 1 . Both groups also showed that overexpression of Tsc1 and Tsc2 resulted in decreased cell number, cell size, and organ size and prolonged the amount of time the cells spent in G 1 . Genetic interactions among cyclins D, E, A; the cyclin-dependent kinase 4; and Tsc1 and Tsc2 were observed by Tapon et al. Genetic interactions, reported by both Tapon et al. and Potter et al. , between various elements of the insulin signaling pathway and Tsc1 and Tsc2 were also seen, suggesting that the TSC complex is a negative regulator of the insulin signaling pathway. N. Tapon, N. Ito, B. J. Dickson, J. E. Treisman, I. K. Hariharan, The Drosophila tuberous sclerosis complex gene homologs restrict cell growth and cell proliferation. Cell 105 , 345-355 (2001). [Online Journal] C. J. Potter, H. Huang, T. Xu, Drosophila Tsc1 functions with Tsc2 to antagonize insulin signaling in regulating cell growth, cell proliferation, and organ size. Cell 105 , 357-368 (2001). [Online Journal]