Disease relevance of Tsc1

• Tuberous sclerosis complex (TSC) is a genetic disorder caused by mutations in one of two tumor suppressor genes, TSC1 and TSC2 [1].
• Germline mutations in either TSC1 or TSC2 cause this syndrome, and hamartomas typically display second hit events with loss of the remaining normal allele [2].

High impact information on Tsc1

• In a screen for patterning mutants, we isolated alleles of tsc1, a component of the insulin receptor (InR) growth control pathway [3].
• We find that loss of tsc1 disrupts patterning due to a loss of temporal control of differentiation. tsc1 controls the timing of differentiation downstream or in parallel to the RAS/MAPK pathway [3].
• We have characterized mutations in the Drosophila Tsc1 and Tsc2/gigas genes [4].
• Coexpression of both Tsc1 and Tsc2 restricts tissue growth and reduces cell size and cell proliferation [4].
• Genetic epistasis data are consistent with a model that Tsc1 and Tsc2 function together in the insulin signaling pathway [5].

Biological context of Tsc1

• Overexpression of Tsc1 or Tsc2 alone in the wing and eye has no effect, but co-overexpression leads to a decrease in cell size, cell number, and organ size [5].
• Drosophila Tsc1 functions with Tsc2 to antagonize insulin signaling in regulating cell growth, cell proliferation, and organ size [5].
• Clones of Tsc1 mutant cells in the imaginal discs undergo additional divisions but retain normal ploidy [5].
• Unlike previous studies, our work shows that TSC1(-) or TSC2(-) cells are diploid [6].
• TSC1 downregulates the insulin-mediated signal transduction pathway, and serves as a metabolic control to guard against cellular overproliferation and tumorogenesis in both flies and mammals [7].

Anatomical context of Tsc1

• In cortical neurons, Pam co-localizes with tuberin and hamartin in neurites and growth cones [8].

Associations of Tsc1 with chemical compounds

• Tuberin and hamartin function together as a complex in mammals and Drosophila [8].

References