A defect in protein farnesylation suppresses a loss of Schizosaccharomyces pombe tsc2+, a homolog of the human gene predisposing to tuberous sclerosis complex.

Genetics
Yukiko NakaseTomohiro Matsumoto

Abstract

Mutations in the human Tsc1 and Tsc2 genes predispose to tuberous sclerosis complex (TSC), a disorder characterized by the wide spread of benign tumors. Tsc1 and Tsc2 proteins form a complex and serve as a GTPase-activating protein (GAP) for Rheb, a GTPase regulating a downstream kinase, mTOR. The genome of Schizosaccharomyces pombe contains tsc1(+) and tsc2(+), homologs of human Tsc1 and Tsc2, respectively. In this study we analyzed the gene expression profile on a genomewide 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 inv1(+) are more induced. We also demonstrate that a mutation (cpp1-1) in a gene encoding a beta-subunit of a farnesyltransferase 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. On the basis of...Continue Reading

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Sep 21, 2012·The Journal of Biological Chemistry·Hidekazu TakahashiMinoru Yoshida
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