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Drosophila Ribosomal Protein Mutants Control Tissue Growth Non-Autonomously via Effects on the Prothoracic Gland and Ecdysone

Lin, Jane I.; Mitchell, Naomi C.; Kalcina, Marina; Tchoubrieva, Elly; Stewart, Mary J.; Marygold, Steven J.; Walker, Cherryl D.; Thomas, George; Leevers, Sally J.; Pearson, Richard B.; Quinn, Leonie M.; Hannan, Ross D.

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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...[Show more]

dc.contributor.authorLin, Jane I.
dc.contributor.authorMitchell, Naomi C.
dc.contributor.authorKalcina, Marina
dc.contributor.authorTchoubrieva, Elly
dc.contributor.authorStewart, Mary J.
dc.contributor.authorMarygold, Steven J.
dc.contributor.authorWalker, Cherryl D.
dc.contributor.authorThomas, George
dc.contributor.authorLeevers, Sally J.
dc.contributor.authorPearson, Richard B.
dc.contributor.authorQuinn, Leonie M.
dc.contributor.authorHannan, Ross D.
dc.date.accessioned2016-01-25T03:33:56Z
dc.date.available2016-01-25T03:33:56Z
dc.identifier.issn1553-7404
dc.identifier.urihttp://hdl.handle.net/1885/95651
dc.description.abstractThe 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.
dc.description.sponsorshipThis work was supported by grants from the National Health and Medical Research Council (NHMRC) of Australia to RDH (NHMRC grants #251688; #1003270; #509088; #400116, #400114; Senior Research Fellowship #166908), to RBP (NHMRC grant #509087, #400116, #251688; Senior Research Fellowship #509027), and to LMQ (NHMRC grants #400114; #10044791 and #628414); by the Australian Postgraduate Award to JIL; and by funding from Cancer Research UK to SJM, CDW, and SJL.
dc.publisherPublic Library of Science
dc.rights© 2011 Lin et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
dc.sourcePLoS Genetics
dc.subjectanimals
dc.subjectanimals, genetically modified
dc.subjectcell proliferation
dc.subjectcyclin e
dc.subjectdrosophila melanogaster
dc.subjectecdysone
dc.subjectendocrine glands
dc.subjecteye
dc.subjectgene expression regulation, developmental
dc.subjectorganogenesis
dc.subjectphenotype
dc.subjectrna interference
dc.subjectribosomal protein s6
dc.titleDrosophila Ribosomal Protein Mutants Control Tissue Growth Non-Autonomously via Effects on the Prothoracic Gland and Ecdysone
dc.typeJournal article
local.identifier.citationvolume7
dc.date.issued2011-12-15
local.publisher.urlhttp://www.plos.org/
local.type.statusPublished Version
local.contributor.affiliationHannan, R., John Curtin School of Medical Research, The Australian National University
dc.relationhttp://purl.org/au-research/grants/nhmrc/251688
dc.relationhttp://purl.org/au-research/grants/nhmrc/1003270
dc.relationhttp://purl.org/au-research/grants/nhmrc/509088
dc.relationhttp://purl.org/au-research/grants/nhmrc/400116
dc.relationhttp://purl.org/au-research/grants/nhmrc/400114
dc.relationhttp://purl.org/au-research/grants/nhmrc/166908
dc.relationhttp://purl.org/au-research/grants/nhmrc/509087
dc.relationhttp://purl.org/au-research/grants/nhmrc/509027
dc.relationhttp://purl.org/au-research/grants/nhmrc/628414
local.identifier.essn1553-7404
local.bibliographicCitation.issue12
local.bibliographicCitation.startpagee1002408
local.identifier.doi10.1371/journal.pgen.1002408
CollectionsANU Research Publications

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