Fission Yeast TORC1 Promotes Cell Proliferation through Sfp1, a Transcription Factor Involved in Ribosome Biogenesis

REFERENCES

• Wullschleger S, Loewith R, Hall MN. TOR signaling in growth and metabolism. Cell. 2006;124:471–484. doi:10.1016/j.cell.2006.01.016.
   PubMed Web of Science ®Google Scholar
• Loewith R, Hall MN. Target of rapamycin (TOR) in nutrient signaling and growth control. Genetics. 2011;189:1177–1201. doi:10.1534/genetics.111.133363.
   PubMed Web of Science ®Google Scholar
• Yang H, Jiang X, Li B, Yang HJ, Miller M, Yang A, Dhar A, Pavletich NP. Mechanisms of mTORC1 activation by RHEB and inhibition by PRAS40. Nature. 2017;552:368–373. doi:10.1038/nature25023.
   PubMed Web of Science ®Google Scholar
• Inoki K, Li Y, Xu T, Guan K-L. Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling. Genes Dev. 2003;17:1829–1834. doi:10.1101/gad.1110003.
   PubMed Web of Science ®Google Scholar
• Inoki K, Li Y, Zhu T, Wu J, Guan K-L. TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling. Nat Cell Biol. 2002;4:648–657. doi:10.1038/ncb839.
   PubMed Web of Science ®Google Scholar
• Bar-Peled L, Schweitzer LD, Zoncu R, Sabatini DM. Ragulator is a GEF for the Rag GTPases that signal amino acid levels to mTORC1. Cell. 2012;150:1196–1208. doi:10.1016/j.cell.2012.07.032.
   PubMed Web of Science ®Google Scholar
• Sancak Y, Bar-Peled L, Zoncu R, Markhard AL, Nada S, Sabatini DM. Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids. Cell. 2010;141:290–303. doi:10.1016/j.cell.2010.02.024.
   PubMed Web of Science ®Google Scholar
• Sancak Y, Peterson TR, Shaul YD, Lindquist RA, Thoreen CC, Bar-Peled L, Sabatini DM. The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1. Science. 2008;320:1496–1501. doi:10.1126/science.1157535.
   PubMed Web of Science ®Google Scholar
• Bar-Peled L, Chantranupong L, Cherniack AD, Chen WW, Ottina KA, Grabiner BC, Spear ED, Carter SL, Meyerson M, Sabatini DM. A Tumor suppressor complex with GAP activity for the Rag GTPases that signal amino acid sufficiency to mTORC1. Science. 2013;340:1100–1106. doi:10.1126/science.1232044.
   PubMed Web of Science ®Google Scholar
• Ben-Sahra I, Manning BD. mTORC1 signaling and the metabolic control of cell growth. Curr Opin Cell Biol. 2017;45:72–82. doi:10.1016/j.ceb.2017.02.012.
   PubMed Web of Science ®Google Scholar
• Ma XM, Blenis J. Molecular mechanisms of mTOR-mediated translational control. Nat Rev Mol Cell Biol. 2009;10:307–318. doi:10.1038/nrm2672.
   PubMed Web of Science ®Google Scholar
• Peterson TR, Sengupta SS, Harris TE, Carmack AE, Kang SA, Balderas E, Guertin DA, Madden KL, Carpenter AE, Finck BN, et al. mTOR Complex 1 regulates Lipin 1 localization to control the SREBP pathway. Cell. 2011;146:408–420. doi:10.1016/j.cell.2011.06.034.
   PubMed Web of Science ®Google Scholar
• Ganley IG, Lam DH, Wang J, Ding X, Chen S, Jiang X. ULK1.ATG13.FIP200 complex mediates mTOR signaling and is essential for autophagy. J Biol Chem. 2009;284:12297–12305. doi:10.1074/jbc.M900573200.
   PubMed Web of Science ®Google Scholar
• Hosokawa N, Hara T, Kaizuka T, Kishi C, Takamura A, Miura Y, Iemura S, Natsume T, Takehana K, Yamada N, et al. Nutrient-dependent mTORC1 association with the ULK1-Atg13-FIP200 complex required for autophagy. Mol Biol Cell. 2009;20:1981–1991. doi:10.1091/mbc.e08-12-1248.
   PubMed Web of Science ®Google Scholar
• Kim LC, Cook RS, Chen J. MTORC1 and mTORC2 in cancer and the tumor microenvironment. Oncogene. 2017;36:2191–2201. doi:10.1038/onc.2016.363.
   PubMed Web of Science ®Google Scholar
• Fukuda T, Shiozaki K. The Rag GTPase-Ragulator complex attenuates TOR complex 1 signaling in fission yeast. Autophagy. 2018;14:1105–1106. doi:10.1080/15548627.2018.1444313.
   PubMed Web of Science ®Google Scholar
• Fukuda T, Shiozaki K. Multiplexed suppression of TOR complex 1 induces autophagy during starvation. Autophagy. 2021;17:1794–1795. doi:10.1080/15548627.2021.1938915.
   PubMed Web of Science ®Google Scholar
• Hayashi T, Hatanaka M, Nagao K, Nakaseko Y, Kanoh J, Kokubu A, Ebe M, Yanagida M. Rapamycin sensitivity of the Schizosaccharomyces pombe tor2 mutant and organization of two highly phosphorylated TOR complexes by specific and common subunits. Genes Cells. 2007;12:1357–1370. doi:10.1111/j.1365-2443.2007.01141.x.
   PubMed Web of Science ®Google Scholar
• Matsuo T, Otsubo Y, Urano J, Tamanoi F, Yamamoto M. Loss of the TOR kinase Tor2 mimics nitrogen starvation and activates the sexual development pathway in fission yeast. Mol Cell Biol. 2007;27:3154–3164. doi:10.1128/MCB.01039-06.
   PubMed Web of Science ®Google Scholar
• Otsubo Y, Nakashima A, Yamamoto M, Yamashita A. TORC1-dependent phosphorylation targets in fission yeast. Biomolecules. 2017;7:50. doi:10.3390/biom7030050.
   PubMed Web of Science ®Google Scholar
• Álvarez B, Moreno S. Fission yeast Tor2 promotes cell growth and represses cell differentiation. J Cell Sci. 2006;119:4475–4485. doi:10.1242/jcs.03241.
   PubMed Web of Science ®Google Scholar
• Uritani M, Hidaka H, Hotta Y, Ueno M, Ushimaru T, Toda T. Fission yeast Tor2 links nitrogen signals to cell proliferation and acts downstream of the Rheb GTPase. Genes Cells. 2006;11:1367–1379. doi:10.1111/j.1365-2443.2006.01025.x.
   PubMed Web of Science ®Google Scholar
• Weisman R, Roitburg I, Schonbrun M, Harari R, Kupiec M. Opposite effects of Tor1 and Tor2 on nitrogen starvation responses in fission yeast. Genetics. 2007;175:1153–1162. doi:10.1534/genetics.106.064170.
   PubMed Web of Science ®Google Scholar
• Nakashima A, Sato T, Tamanoi F. Fission yeast TORC1 regulates phosphorylation of ribosomal S6 proteins in response to nutrients and its activity is inhibited by rapamycin. J Cell Sci. 2010;123:777–786. doi:10.1242/jcs.060319.
   PubMed Web of Science ®Google Scholar
• Nakashima A, Otsubo Y, Yamashita A, Sato T, Yamamoto M, Tamanoi F. Psk1, an AGC kinase family member in fission yeast, is directly phosphorylated and controlled by TORC1 and functions as S6 kinase. J Cell Sci. 2012;125:5840–5849. doi:10.1242/jcs.111146.
   PubMed Web of Science ®Google Scholar
• Tanaka K, Yonekawa T, Kawasaki Y, Kai M, Furuya K, Iwasaki M, Murakami H, Yanagida M, Okayama H. Fission yeast Eso1p is required for establishing sister chromatid cohesion during S phase. Mol Cell Biol. 2000;20:3459–3469. doi:10.1128/MCB.20.10.3459-3469.2000.
   PubMed Web of Science ®Google Scholar
• Cipollina C, Alberghina L, Porro D, Vai M. SFP1 is involved in cell size modulation in respiro-fermentative growth conditions. Yeast. 2005;22:385–399. doi:10.1002/yea.1218.
   PubMed Web of Science ®Google Scholar
• Chia KH, Fukuda T, Sofyantoro F, Matsuda T, Amai T, Shiozaki K. Ragulator and GATOR1 complexes promote fission yeast growth by attenuating TOR complex 1 through Rag GTPases. elife. 2017;6:e30880. doi:10.7554/eLife.30880.
   PubMed Web of Science ®Google Scholar
• Kohda TA, Tanaka K, Konomi M, Sato M, Osumi M, Yamamoto M. Fission yeast autophagy induced by nitrogen starvation generates a nitrogen source that drives adaptation processes. Genes Cells. 2007;12:155–170. doi:10.1111/j.1365-2443.2007.01041.x.
   PubMed Web of Science ®Google Scholar
• Nakashima A, Hasegawa T, Mori S, Ueno M, Tanaka S, Ushimaru T, Sato S, Uritani M. A starvation-specific serine protease gene, isp6+, is involved in both autophagy and sexual development in Schizosaccharomyces pombe. Curr Genet. 2006;49:403–413. doi:10.1007/s00294-006-0067-0.
   PubMed Web of Science ®Google Scholar
• Marguerat S, Schmidt A, Codlin S, Chen W, Aebersold R, Bähler J. Quantitative analysis of fission yeast transcriptomes and proteomes in proliferating and quiescent cells. Cell. 2012;151:671–683. doi:10.1016/j.cell.2012.09.019.
   PubMed Web of Science ®Google Scholar
• Gordon C, McGurk G, Wallace M, Hastie ND. A conditional lethal mutant in the fission yeast 26 S protease subunit mts3+ is defective in metaphase to anaphase transition. J Biol Chem. 1996;271:5704–5711. doi:10.1074/jbc.271.10.5704.
   PubMed Web of Science ®Google Scholar
• Takeda K, Mori A, Yanagida M. Identification of genes affecting the toxicity of anti-cancer drug Bortezomib by genome-wide screening in S. pombe. PLoS One. 2011;6:e22021. doi:10.1371/journal.pone.0022021.
   PubMed Web of Science ®Google Scholar
• Warner JR. The economics of ribosome biosynthesis in yeast. Trends Biochem Sci. 1999;24:437–440. doi:10.1016/S0968-0004(99)01460-7.
   PubMed Web of Science ®Google Scholar
• Jorgensen P, Rupes I, Sharom JR, Schneper L, Broach JR, Tyers M. A dynamic transcriptional network communicates growth potential to ribosome synthesis and critical cell size. Genes Dev. 2004;18:2491–2505. doi:10.1101/gad.1228804.
   PubMed Web of Science ®Google Scholar
• Martin DE, Soulard A, Hall MN. TOR regulates ribosomal protein gene expression via PKA and the Forkhead transcription factor FHL1. Cell. 2004;119:969–979. doi:10.1016/j.cell.2004.11.047.
   PubMed Web of Science ®Google Scholar
• Zencir S, Dilg D, Rueda MP, Shore D, Albert B. Mechanisms coordinating ribosomal protein gene transcription in response to stress. Nucleic Acids Res. 2020;48:11408–11420. doi:10.1093/nar/gkaa852.
   PubMed Web of Science ®Google Scholar
• Wapinski I, Pfiffner J, French C, Socha A, Thompson DA, Regev A. Gene duplication and the evolution of ribosomal protein gene regulation in yeast. Proc Natl Acad Sci USA. 2010;107:5505–5510. doi:10.1073/pnas.0911905107.
   PubMed Web of Science ®Google Scholar
• Kim MS, Hahn J-S. Role of CK2-dependent phosphorylation of Ifh1 and Crf1 in transcriptional regulation of ribosomal protein genes in Saccharomyces cerevisiae. Biochim Biophys Acta. 2016;1859:1004–1013. doi:10.1016/j.bbagrm.2016.06.003.
   PubMed Web of Science ®Google Scholar
• Pataki E, Weisman R, Sipiczki M, Miklos I. fhl1 gene of the fission yeast regulates transcription of meiotic genes and nitrogen starvation response, downstream of the TORC1 pathway. Curr Genet. 2017;63:91–101. doi:10.1007/s00294-016-0607-1.
   PubMed Web of Science ®Google Scholar
• Shetty M, Noguchi C, Wilson S, Martinez E, Shiozaki K, Sell C, Mell JC, Noguchi E. Maf1-dependent transcriptional regulation of tRNAs prevents genomic instability and is associated with extended lifespan. Aging Cell. 2020;19:e13068. doi:10.1111/acel.13068.
   PubMed Web of Science ®Google Scholar
• Albert B, Tomassetti S, Gloor Y, Dilg D, Mattarocci S, Kubik S, Hafner L, Shore D. Sfp1 regulates transcriptional networks driving cell growth and division through multiple promoter-binding modes. Genes Dev. 2019;33:288–293. doi:10.1101/gad.322040.118.
   PubMed Web of Science ®Google Scholar
• Fingerman I, Nagaraj V, Norris D, Vershon AK. Sfp1 plays a key role in yeast ribosome biogenesis. Eukaryot Cell. 2003;2:1061–1068. doi:10.1128/EC.2.5.1061-1068.2003.
   PubMed Web of Science ®Google Scholar
• Marion RM, Regev A, Segal E, Barash Y, Koller D, Friedman N, O'Shea EK. Sfp1 is a stress- and nutrient-sensitive regulator of ribosomal protein gene expression. Proc Natl Acad Sci USA. 2004;101:14315–14322. doi:10.1073/pnas.0405353101.
   PubMed Web of Science ®Google Scholar
• Hirai H, Ohta K. Comparative research: regulatory mechanisms of ribosomal gene transcription in Saccharomyces cerevisiae and Schizosaccharomyces pombe. Biomolecules. 2023;13:288. doi:10.3390/biom13020288.
   PubMed Web of Science ®Google Scholar
• Lempiäinen H, Uotila A, Urban J, Dohnal I, Ammerer G, Loewith R, Shore D. Sfp1 interaction with TORC1 and Mrs6 reveals feedback regulation on TOR signaling. Mol Cell. 2009;33:704–716. doi:10.1016/j.molcel.2009.01.034.
   PubMed Web of Science ®Google Scholar
• Singh J, Tyers M. A Rab escort protein integrates the secretion system with TOR signaling and ribosome biogenesis. Genes Dev. 2009;23:1944–1958. doi:10.1101/gad.1804409.
   PubMed Web of Science ®Google Scholar
• Jorgensen P, Nishikawa JL, Breitkreutz B-J, Tyers M. Systematic identification of pathways that couple cell growth and division in yeast. Science. 2002;297:395–400. doi:10.1126/science.1070850.
   PubMed Web of Science ®Google Scholar
• Zhou D-z, Liu Y, Zhang D, Liu S-m, Yu L, Yang Y-f, Zhao T, Chen Z, Kan M-y, Zhang Z-f, et al. Variations in/nearby genes coding for JAZF1, TSPAN8/LGR5 and HHEX-IDE and risk of type 2 diabetes in Han Chinese. J Hum Genet. 2010;55:810–815. doi:10.1038/jhg.2010.117.
   PubMed Web of Science ®Google Scholar
• Alharbi KK, Ali Khan I, Syed R, Alharbi FK, Mohammed AK, Vinodson B, Al-Daghri NM. Association of JAZF1 and TSPAN8/LGR5 variants in relation to type 2 diabetes mellitus in a Saudi population. Diabetol Metab Syndr. 2015;7:92. doi:10.1186/s13098-015-0091-7.
   PubMed Web of Science ®Google Scholar
• Sung Y, Park S, Park SJ, Jeong J, Choi M, Lee J, Kwon W, Jang S, Lee M-H, Kim DJ, et al. Jazf1 promotes prostate cancer progression by activating JNK/Slug. Oncotarget. 2018;9:755–765. doi:10.18632/oncotarget.23146.
   PubMedGoogle Scholar
• Kobiita A, Godbersen S, Araldi E, Ghoshdastider U, Schmid MW, Spinas G, Moch H, Stoffel M. The diabetes gene JAZF1 is essential for the homeostatic control of ribosome biogenesis and function in metabolic stress. Cell Rep. 2020;32:107846. doi:10.1016/j.celrep.2020.107846.
   PubMed Web of Science ®Google Scholar
• Dai X, Zhu M. Coupling of ribosome synthesis and translational capacity with cell growth. Trends Biochem Sci. 2020;45:681–692. doi:10.1016/j.tibs.2020.04.010.
   PubMed Web of Science ®Google Scholar
• Kelly SP, Bedwell DM. Both the autophagy and proteasomal pathways facilitate the Ubp3p-dependent depletion of a subset of translation and RNA turnover factors during nitrogen starvation in Saccharomyces cerevisiae. RNA. 2015;21:898–910. doi:10.1261/rna.045211.114.
   PubMed Web of Science ®Google Scholar
• Reja R, Vinayachandran V, Ghosh S, Pugh BF. Molecular mechanisms of ribosomal protein gene coregulation. Genes Dev. 2015;29:1942–1954. doi:10.1101/gad.268896.115.
   PubMed Web of Science ®Google Scholar
• Schawalder S, Kabani M, Howald I, Choudhury U, Werner M, Shore D. Growth-regulated recruitment of the essential yeast ribosomal protein gene activator Ifh1. Nature. 2004;432:1058–1061. doi:10.1038/nature03200.
   PubMed Web of Science ®Google Scholar
• Rudra D, Zhao Y, Warner JR. Central role of Ifh1p–Fhl1p interaction in the synthesis of yeast ribosomal proteins. EMBO J. 2005;24:533–542. doi:10.1038/sj.emboj.7600553.
   PubMed Web of Science ®Google Scholar
• Wade J, Hall D, Struhl K. The transcription factor Ifh1 is a key regulator of yeast ribosomal protein genes. Nature. 2004;432:1054–1058. doi:10.1038/nature03175.
   PubMed Web of Science ®Google Scholar
• Lee TI, Rinaldi NJ, Robert F, Odom DT, Bar-Joseph Z, Gerber GK, Hannett NM, Harbison CT, Thompson CM, Simon I, et al. Transcriptional regulatory networks in Saccharomyces cerevisiae. Science. 2002;298:799–804. doi:10.1126/science.1075090.
   PubMed Web of Science ®Google Scholar
• Albert B, Kos-Braun IC, Henras AK, Dez C, Rueda MP, Zhang X, Gadal O, Kos M, Shore D. A ribosome assembly stress response regulates transcription to maintain proteome homeostasis. Elife. 2019;8:e45002. doi:10.7554/eLife.45002.
   PubMed Web of Science ®Google Scholar
• Kasahara K, Nakayama R, Shiwa Y, Kanesaki Y, Ishige T, Yoshikawa H, Kokubo T. Fpr1, a primary target of rapamycin, functions as a transcription factor for ribosomal protein genes cooperatively with Hmo1 in Saccharomyces cerevisiae. PLoS Genet. 2020;16:e1008865. doi:10.1371/journal.pgen.1008865.
   PubMed Web of Science ®Google Scholar
• Freed EF, Bleichert F, Dutca LM, Baserga SJ. When ribosomes go bad: diseases of ribosome biogenesis. Mol Biosyst. 2010;6:481–493. doi:10.1039/b919670f.
   PubMed Web of Science ®Google Scholar
• Pelletier J, Thomas G, Volarević S. Ribosome biogenesis in cancer: new players and therapeutic avenues. Nat Rev Cancer. 2018;18:51–63. doi:10.1038/nrc.2017.104.
   PubMed Web of Science ®Google Scholar
• Morozumi Y, Shiozaki K. Conserved and divergent mechanisms that control TORC1 in yeasts and mammals. Genes (Basel). 2021;12:88. doi:10.3390/genes12010088.
   PubMed Web of Science ®Google Scholar
• Fukuda T, Sofyantoro F, Tai YT, Chia KH, Matsuda T, Murase T, Morozumi Y, Tatebe H, Kanki T, Shiozaki K. Tripartite suppression of fission yeast TORC1 signaling by the GATOR1-Sea3 complex, the TSC complex, and Gcn2 kinase. elife. 2021;10:e60969. doi:10.7554/eLife.60969.
   PubMed Web of Science ®Google Scholar
• Kunitomo H, Sugimoto A, Wilkinson C, Yamamoto M. Schizosaccharomyces pombe pac2+ controls the onset of sexual development via a pathway independent of the cAMP cascade. Curr Genet. 1995;28:32–38. doi:10.1007/BF00311879.
   PubMed Web of Science ®Google Scholar
• Morigasaki S, Chin LC, Hatano T, Emori M, Iwamoto M, Tatebe H, Shiozaki K. Modulation of TOR complex 2 signaling by the stress-activated MAPK pathway in fission yeast. J Cell Sci. 2019;132:jcs236133. doi:10.1242/jcs.236133.
   PubMed Web of Science ®Google Scholar
• Tatebe H, Shiozaki K. Identification of Cdc37 as a novel regulator of the stress-responsive mitogen-activated protein kinase. Mol Cell Biol. 2003;23:5132–5142. doi:10.1128/MCB.23.15.5132-5142.2003.
   PubMed Web of Science ®Google Scholar
• Kamada Y, Ando R, Izawa S, Matsuura A. Yeast Tor complex 1 phosphorylates eIF4E-binding protein, Caf20. Genes Cells. 2023;28:789–799. doi:10.1111/gtc.13067.
   PubMedGoogle Scholar
• Otsubo Y, Yamashita A, Ohno H, Yamamoto M. S. pombe TORC1 activates the ubiquitin-proteasomal degradation of the meiotic regulator Mei2 in cooperation with Pat1 kinase. J Cell Sci. 2014;127:2639–2646. doi:10.1242/jcs.135517.
   PubMed Web of Science ®Google Scholar
• Kim D, Pertea G, Trapnell C, Pimentel H, Kelley R, Salzberg SL. TopHat2: Accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome Biol. 2013;14:R36. doi:10.1186/gb-2013-14-4-r36.
   PubMed Web of Science ®Google Scholar
• Roberts A, Trapnell C, Donaghey J, Rinn JL, Pachter L. Improving RNA-Seq expression estimates by correcting for fragment bias. Genome Biol. 2011;12:R22. doi:10.1186/gb-2011-12-3-r22.
   PubMed Web of Science ®Google Scholar
• Trapnell C, Williams BA, Pertea G, Mortazavi A, Kwan G, Van Baren MJ, Salzberg SL, Wold BJ, Pachter L. Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation. Nat Biotechnol. 2010;28:511–515. doi:10.1038/nbt.1621.
   PubMed Web of Science ®Google Scholar
• Harris MA, Rutherford KM, Hayles J, Lock A, Bähler J, Oliver SG, Mata J, Wood V. Fission stories: using PomBase to understand Schizosaccharomyces pombe biology. Genetics. 2022;220:iyab222. doi:10.1093/genetics/iyab222.
   PubMed Web of Science ®Google Scholar
• Wickham H. ggplot2: elegant graphics for data analysis. New York (NY): Springer-Verlag; 2016. doi:10.1007/978-3-319-24277-4.
   Google Scholar
• Hirai H, Takemata N, Tamura M, Ohta K. Facultative heterochromatin formation in rDNA is essential for cell survival during nutritional starvation. Nucleic Acids Res. 2022;50:3727–3744. doi:10.1093/nar/gkac175.
   PubMed Web of Science ®Google Scholar
• Martin M. Cutadapt removes adapter sequences from high-throughput sequencing reads. EMBnet J. 2011;17:10–12. doi:10.14806/ej.17.1.200.
   Google Scholar
• Langmead B, Salzberg SL. Fast gapped-read alignment with Bowtie 2. Nat Methods. 2012;9:357–359. doi:10.1038/nmeth.1923.
   PubMed Web of Science ®Google Scholar
• Zhang Y, Liu T, Meyer CA, Eeckhoute J, Johnson DS, Bernstein BE, Nusbaum C, Myers RM, Brown M, Li W, et al. Model-based analysis of ChIP-Seq (MACS). Genome Biol. 2008;9:R137. doi:10.1186/gb-2008-9-9-r137.
   PubMed Web of Science ®Google Scholar
• Robinson JT, Thorvaldsdóttir H, Winckler W, Guttman M, Lander ES, Getz G, Mesirov JP. Integrative genomics viewer. Nat Biotechnol. 2011;29:24–26. doi:10.1038/nbt.1754.
   PubMed Web of Science ®Google Scholar