Linked Life Data

16115814

Source:http://linkedlifedata.com/resource/pubmed/id/16115814

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
19
pubmed:dateCreated
2005-9-16
pubmed:abstractText
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 Deltatsc1. Disruption of pas1+ causes defects in arginine and leucine uptake that are remarkably similar to Deltatsc1 and Deltatsc2, whereas Deltapas1Deltatsc1 and Deltapas1Deltatsc2 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 Deltatsc1 yeast, but not in Deltapas1 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, Deltatsc1 and Deltatsc2 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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Triphosphatases, http://linkedlifedata.com/resource/pubmed/chemical/Arginine, http://linkedlifedata.com/resource/pubmed/chemical/Canavanine, http://linkedlifedata.com/resource/pubmed/chemical/Cyclins, http://linkedlifedata.com/resource/pubmed/chemical/Fungal Proteins, http://linkedlifedata.com/resource/pubmed/chemical/GTP Phosphohydrolases, http://linkedlifedata.com/resource/pubmed/chemical/Leucine, http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Rhb1 protein, S pombe, http://linkedlifedata.com/resource/pubmed/chemical/Schizosaccharomyces pombe Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Tsc1 protein, S pombe, http://linkedlifedata.com/resource/pubmed/chemical/Tsc2 protein, S pombe, http://linkedlifedata.com/resource/pubmed/chemical/pas1 protein, S pombe
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0964-6906
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
14
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2851-8
pubmed:dateRevised
2007-11-19
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Pas1, a G1 cyclin, regulates amino acid uptake and rescues a delay in G1 arrest in Tsc1 and Tsc2 mutants in Schizosaccharomyces pombe.
pubmed:affiliation
Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't