title: Drosophila ribosomal protein mutants control tissue growth non-autonomously via effects on the prothoracic gland and ecdysone.
abstract: The ribosome is critical for all aspects of cell growth due to its essential role in protein synthesis. Paradoxically, many Ribosomal proteins (Rps) act as tumour suppressors in Drosophila and vertebrates. To examine how reductions in Rps could lead to tissue overgrowth, we took advantage of the observation that an RpS6 mutant dominantly suppresses the small rough eye phenotype in a cyclin E hypomorphic mutant (cycE(JP)). We demonstrated that the suppression of cycE(JP) by the RpS6 mutant is not a consequence of restoring CycE protein levels or activity in the eye imaginal tissue. Rather, the use of UAS-RpS6 RNAi transgenics revealed that the suppression of cycE(JP) is exerted via a mechanism extrinsic to the eye, whereby reduced Rp levels in the prothoracic gland decreases the activity of ecdysone, the steroid hormone, delaying developmental timing and hence allowing time for tissue and organ overgrowth. These data provide for the first time a rationale to explain the counter-intuitive organ overgrowth phenotypes observed for certain members of the Minute class of Drosophila Rp mutants. They also demonstrate how Rp mutants can affect growth and development cell non-autonomously.
authors.affiliation: Peter MacCallum Cancer Centre, East Melbourne, Australia.
authors.forename: Jane I
authors.initials: JI
authors.lastname: Lin
authors.forename: Naomi C
authors.initials: NC
authors.lastname: Mitchell
authors.forename: Marina
authors.initials: M
authors.lastname: Kalcina
authors.forename: Elly
authors.initials: E
authors.lastname: Tchoubrieva
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Stewart
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Marygold
authors.forename: Cherryl D
authors.initials: CD
authors.lastname: Walker
authors.forename: George
authors.initials: G
authors.lastname: Thomas
authors.forename: Sally J
authors.initials: SJ
authors.lastname: Leevers
authors.forename: Richard B
authors.initials: RB
authors.lastname: Pearson
authors.forename: Leonie M
authors.initials: LM
authors.lastname: Quinn
authors.forename: Ross D
authors.initials: RD
authors.lastname: Hannan
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D049109:Cell Proliferation; D019927:Cyclin E / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics* / Q000254:growth & development* / Q000378:metabolism; D004440:Ecdysone / Q000378:metabolism*; D004702:Endocrine Glands / Q000378:metabolism; D005123:Eye / Q000254:growth & development* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D038081:Organogenesis / Q000235:genetics; D010641:Phenotype; D034622:RNA Interference; D038601:Ribosomal Protein S6 / Q000235:genetics* / Q000378:metabolism
chemical_list: D019927:Cyclin E; D038601:Ribosomal Protein S6; D004440:Ecdysone