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PMID:22555454

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Citation

Verghese, S, Bedi, S and Kango-Singh, M (2012) Hippo signalling controls Dronc activity to regulate organ size in Drosophila. Cell Death Differ. 19:1664-76

Abstract

The Hippo pathway controls organ size by multiple mechanisms that ultimately regulate the transcriptional co-activator Yorkie (Yki). Downregulation of Hippo signalling leads to tissue overgrowths due to Yki-mediated activation of target genes, whereas overexpression of the pathway triggers apoptosis in developing tissues. However, the mechanism underlying cell death induced by Hippo (Hpo)-activation is not understood. We found that overexpression of Hpo leads to induction of Dronc (Drosophila Caspase-9 homologue) expression and downregulation of dronc can suppress/block Hpo-mediated apoptosis. Furthermore, upregulation of Dronc activity strongly suppressed the overgrowth caused by Yki overexpression thereby suggesting that Hippo signalling restricts Dronc activity. Hippo-mediated cell death requires the activity of the initiator caspase Dronc. Loss-of-function of dronc in genetic mosaics leads to cell survival and increased cell proliferation in imaginal discs. dronc is transcriptionally suppressed in Yki overexpressing cells or cells mutant for other Hippo pathway components like warts (wts). We propose that Dronc is a transcriptional target of the Hippo signalling pathway. The Hippo-Dronc connection has implications in control of overall organ size and other growth regulatory mechanisms like compensatory proliferation and cell competition.

Links

PubMed PMC3438497 Online version:10.1038/cdd.2012.48

Keywords

Animals; Apoptosis; Caspases/metabolism; Cell Proliferation; Cell Survival; Down-Regulation; Drosophila/growth & development; Drosophila/metabolism; Drosophila Proteins/genetics; Drosophila Proteins/metabolism; Intracellular Signaling Peptides and Proteins/genetics; Intracellular Signaling Peptides and Proteins/metabolism; Nuclear Proteins/metabolism; Organ Size; Protein-Serine-Threonine Kinases/genetics; Protein-Serine-Threonine Kinases/metabolism; Signal Transduction; Trans-Activators/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

DROME:HIPPO

involved_in

GO:0035265: organ growth

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:DRONC

involved_in

GO:0008285: negative regulation of cell population proliferation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:ICENC

involved_in

GO:0008285: negative regulation of cell population proliferation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

See also

References

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Internal error - GONUTS

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Internal error

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[13d34aa74c9527f0b7f8e1ed] /wiki/index.php/PMID:22555454 Error from line 252 of /usr/local/github/wiki-extensions/wiki-extensions-hulab/AnnotationLinks/AnnotationLinks.php: Call to a member function getIdentifier() on null

Backtrace:

#0 /usr/local/github/wiki-extensions/wiki-extensions-hulab/AnnotationLinks/AnnotationLinks.php(70): AnnotationLinks::getQuickGOannotations(string, array)
#1 /var/www/html/go/wiki/includes/parser/Parser.php(3888): AnnotationLinks::renderAnnotations(NULL, array, Parser, PPFrame_DOM)
#2 /var/www/html/go/wiki/includes/parser/Preprocessor_DOM.php(1362): Parser->extensionSubstitution(array, PPFrame_DOM)
#3 /var/www/html/go/wiki/includes/parser/Parser.php(2942): PPFrame_DOM->expand(DOMElement, integer)
#4 /var/www/html/go/wiki/includes/parser/Parser.php(1293): Parser->replaceVariables(string)
#5 /var/www/html/go/wiki/includes/parser/Parser.php(443): Parser->internalParse(string)
#6 /var/www/html/go/wiki/includes/content/WikitextContent.php(323): Parser->parse(string, Title, ParserOptions, boolean, boolean, integer)
#7 /var/www/html/go/wiki/includes/content/AbstractContent.php(516): WikitextContent->fillParserOutput(Title, integer, ParserOptions, boolean, ParserOutput)
#8 /var/www/html/go/wiki/includes/jobqueue/jobs/RefreshLinksJob.php(231): AbstractContent->getParserOutput(Title, integer, ParserOptions, boolean)
#9 /var/www/html/go/wiki/includes/jobqueue/jobs/RefreshLinksJob.php(126): RefreshLinksJob->runForTitle(Title)
#10 /var/www/html/go/wiki/includes/jobqueue/JobRunner.php(296): RefreshLinksJob->run()
#11 /var/www/html/go/wiki/includes/jobqueue/JobRunner.php(193): JobRunner->executeJob(RefreshLinksJob, Wikimedia\Rdbms\LBFactorySimple, BufferingStatsdDataFactory, integer)
#12 /var/www/html/go/wiki/includes/MediaWiki.php(1002): JobRunner->run(array)
#13 /var/www/html/go/wiki/includes/MediaWiki.php(988): MediaWiki->triggerSyncJobs(integer, MediaWiki\Logger\LegacyLogger)
#14 /var/www/html/go/wiki/includes/MediaWiki.php(912): MediaWiki->triggerJobs()
#15 /var/www/html/go/wiki/includes/MediaWiki.php(727): MediaWiki->restInPeace(string, boolean)
#16 /var/www/html/go/wiki/includes/MediaWiki.php(750): MediaWiki->{closure}()
#17 /var/www/html/go/wiki/includes/MediaWiki.php(557): MediaWiki->doPostOutputShutdown(string)
#18 /var/www/html/go/wiki/index.php(42): MediaWiki->run()
#19 {main}

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