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A defect in protein farnesylation suppresses a loss of fission yeast tsc2

ABSTRACT: Human Tsc1 and Tsc2 genes predispose to Tuberous Sclerosis Complex (TSC), a disorder characterized by the widespread of benign tumors. Tsc1 and Tsc2 proteins form a complex and serve as a GAP (GTP activating protein) for Rheb, a GTPase regulating a downstream kinase, mTor. The fission yeast genome contains tsc1+ and tsc2+, homologs of human Tsc1and Tsc2, respectively. In this study we analyzed gene expression profile in a genome-wide scale and found that deletion of either tsc1+ or tsc2+ affects gene induction upon nitrogen starvation. Three hours after nitrogen depletion genes encoding permeases and genes required for meiosis are less induced. Under the same condition, retrotransposons, G1-cyclin (pas1+) and a gene normally repressed by glucose (inv1+) are more induced. We also demonstrate that a mutation (cpp1-1) in a gene encoding aβ-subunit of a farnesyl transferase can suppress most of the phenotypes associated with deletion of tsc1+ or tsc2+. When a mutant of rhb1+ (homolog of human Rheb), which bypasses the requirement of protein farnesylation, was expressed, the cpp1-1 mutation could no longer suppress, indicating that deficient farnesylation of Rhb1 contributes to the suppression. Based on these results, we discuss the TSC-pathology and possible improvement in chemotherapy for TSC. Keywords: Keywards: Nitrogen starvation, Dtsc1. Dtsc2

ORGANISM(S): Schizosaccharomyces pombe

PROVIDER: GSE4449 | GEO | 2006/06/13

SECONDARY ACCESSION(S): PRJNA94721

REPOSITORIES: GEO

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