{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T14:00:45Z","timestamp":1753884045994,"version":"3.41.2"},"reference-count":63,"publisher":"The Company of Biologists","license":[{"start":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T00:00:00Z","timestamp":1621296000000},"content-version":"am","delay-in-days":1598,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0"}],"funder":[{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["W81XWH-14-1-0169"],"award-info":[{"award-number":["W81XWH-14-1-0169"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Tuberous sclerosis complex is an autosomal dominant disorder characterized by benign tumors arising from the abnormal activation of mTOR signaling in cells lacking TSC1 (hamartin) or TSC2 (tuberin) activity. To expand the genetic framework surrounding this group of growth regulators, we utilized the model eukaryote Schizosaccharomyces pombe to uncover and characterize genes that buffer the phenotypic effects of mutations in the orthologous tsc1 or tsc2 loci. Our study identified two genes: fft3 (encoding a DNA helicase) and ypa1 (encoding a peptidyle-prolyl cis\/trans isomerase). While the deletion of fft3 or ypa1 has little effect in wild-type fission yeast cells, their loss in tsc1\u0394 or tsc2\u0394 backgrounds results in severe growth inhibition. These data suggest that the inhibition of Ypa1p or Fft3p might represent an \u201cAchilles\u2019 heel\u201d of cells defective in hamartin\/tuberin function. Furthermore, we demonstrate that the interaction between tsc1\/tsc2 and ypa1 can be rescued through treatment with the mTOR inhibitor, torin-1, and that ypa1\u0394 cells are resistant to the glycolytic inhibitor, 2-deoxyglucose. This identifies ypa1 as a novel upstream regulator of mTOR and suggests that the effects of ypa1 loss, together with mTOR activation, combine to result in a cellular maladaptation in energy metabolism that is profoundly inhibitory to growth.<\/jats:p>","DOI":"10.1242\/bio.031302","type":"journal-article","created":{"date-parts":[[2018,1,18]],"date-time":"2018-01-18T01:10:34Z","timestamp":1516237834000},"source":"Crossref","is-referenced-by-count":1,"title":["Using genetic buffering relationships identified in fission yeast to reveal susceptibilities in cells lacking hamartin or tuberin function"],"prefix":"10.1242","author":[{"given":"Ashyad","family":"Rayhan","sequence":"first","affiliation":[{"name":"Department of Biology, The University of Western Ontario, London, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam","family":"Faller","sequence":"additional","affiliation":[{"name":"Department of Biology, The University of Western Ontario, London, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryan","family":"Chevalier","sequence":"additional","affiliation":[{"name":"Department of Biology, The University of Western Ontario, London, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alannah","family":"Mattice","sequence":"additional","affiliation":[{"name":"Department of Biology, The University of Western Ontario, London, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7901-1815","authenticated-orcid":false,"given":"Jim","family":"Karagiannis","sequence":"additional","affiliation":[{"name":"Department of Biology, The University of Western Ontario, London, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[2017,1,1]]},"reference":[{"key":"2021042423340834600_BIO031302C1","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1007\/s00438-008-0320-y","article-title":"The Tsc\/Rheb signaling pathway controls basic amino acid uptake via the Cat1 permease in fission yeast","volume":"279","author":"Aspuria","year":"2008","journal-title":"Mol. 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