title: 14-3-3 proteins regulate Tctp-Rheb interaction for organ growth in Drosophila.
abstract: 14-3-3 family proteins regulate multiple signalling pathways. Understanding biological functions of 14-3-3 proteins has been limited by the functional redundancy of conserved isotypes. Here we provide evidence that 14-3-3 proteins regulate two interacting components of Tor signalling in Drosophila, translationally controlled tumour protein (Tctp) and Rheb GTPase. Single knockdown of 14-3-3ɛ or 14-3-3ζ isoform does not show obvious defects in organ development but causes synergistic genetic interaction with Tctp and Rheb to impair tissue growth. 14-3-3 proteins physically interact with Tctp and Rheb. Knockdown of both 14-3-3 isoforms abolishes the binding between Tctp and Rheb, disrupting organ development. Depletion of 14-3-3s also reduces the level of phosphorylated S6 kinase, phosphorylated Thor/4E-BP and cyclin E (CycE). Growth defects from knockdown of 14-3-3 and Tctp are suppressed by CycE overexpression. This study suggests a novel mechanism of Tor regulation mediated by 14-3-3 interaction with Tctp and Rheb.
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 305-701, Korea.
authors.forename: Thao Phuong
authors.initials: TP
authors.lastname: Le
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 305-701, Korea.
authors.forename: Linh Thuong
authors.initials: LT
authors.lastname: Vuong
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 305-701, Korea.
authors.forename: Ah-Ram
authors.initials: AR
authors.lastname: Kim
authors.affiliation: Department of Stem Cell and Regenerative Biology, Harvard University, Sherman Fairchild 358A, 7 Divinity Avenue Cambridge, Massachusetts 02138, USA.
authors.forename: Ya-Chieh
authors.initials: YC
authors.lastname: Hsu
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 305-701, Korea.
authors.forename: Kwang-Wook
authors.initials: KW
authors.lastname: Choi
mesh_terms: D048948:14-3-3 Proteins / Q000235:genetics*; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D004330:Drosophila / Q000196:embryology* / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D055785:Gene Knockdown Techniques; D047908:Intracellular Signaling Peptides and Proteins; D000076205:Ras Homolog Enriched in Brain Protein / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000235:genetics*
chemical_list: D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor; D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D000076205:Ras Homolog Enriched in Brain Protein; C490212:Rheb protein, Drosophila; C517693:TCTP protein, Drosophila; C416303:target of rapamycin protein, Drosophila; D058570:TOR Serine-Threonine Kinases