Journal Article

Pas1, a G<sub>1</sub> cyclin, regulates amino acid uptake and rescues a delay in G<sub>1</sub> arrest in Tsc1 and Tsc2 mutants in <i>Schizosaccharomyces pombe</i>

Marjon van Slegtenhorst, Aladdin Mustafa and Elizabeth Petri Henske

in Human Molecular Genetics

Volume 14, issue 19, pages 2851-2858
Published in print October 2005 | ISSN: 0964-6906
Published online August 2005 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddi317
Pas1, a G1 cyclin, regulates amino acid uptake and rescues a delay in G1 arrest in Tsc1 and Tsc2 mutants in Schizosaccharomyces pombe

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Tuberous sclerosis complex is a tumor suppressor syndrome caused by mutations in either the TSC1 or the TSC2 gene. Previous studies have shown that deletion of the TSC1 or TSC2 ortholog in Schizosaccharomyces pombe results in an amino acid uptake defect, with conditional lethality. We identified a G1 cyclin, pas1+, as a high-copy suppressor of this defect in Δtsc1. Disruption of pas1+ causes defects in arginine and leucine uptake that are remarkably similar to Δtsc1 and Δtsc2, whereas Δpas1Δtsc1 and Δpas1Δtsc2 double mutants have more severe amino acid uptake defects. In a second screen, we identified a novel G63D/S165 N mutant of the small GTPase Rhb1, the target of the Tsc1/Tsc2 protein complex. The Rhb1 mutant suppresses amino acid uptake in Δtsc1 yeast, but not in Δpas1 yeast. Hence, Pas1 does not regulate amino acid uptake through Rhb1. To determine whether Pas1 links nutrient availability to cell cycle progression downstream of the Tsc1/Tsc2 complex, we examined the kinetics of G1 arrest in single and double mutant strains. After nitrogen starvation, Δtsc1 and Δtsc2 yeast had a delay in G1 arrest when compared with wild-type, which was rescued by deletion of pas1+. In summary, we identified the G1 cyclin, Pas1, as a novel regulator of amino acid uptake. Our data support a model in which Pas1 inhibits G1 arrest downstream of Tsc1 and Tsc2, linking nutrient uptake and cell cycle progression in yeast.

Journal Article.  5306 words.  Illustrated.

Subjects: Genetics and Genomics

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