Abstract
The LC8 family of small ~8 kD proteins are highly conserved and interact with multiple protein partners in eukaryotic cells. LC8-binding modulates target protein activity, often through induced dimerization via LC8:LC8 homodimers. Although many LC8-interactors have roles in signaling cascades, LC8's role in developing epithelia is poorly understood. Using the Drosophila wing as a developmental model, we find that the LC8 family member Cut up (Ctp) is primarily required to promote epithelial growth, which correlates with effects on the pro-growth factor dMyc and two genes, diap1 and bantam, that are classic targets of the Hippo pathway coactivator Yorkie. Genetic tests confirm that Ctp supports Yorkie-driven tissue overgrowth and indicate that Ctp acts through Yorkie to control bantam (ban) and diap1 transcription. Quite unexpectedly however, Ctp loss has inverse effects on ban and diap1: it elevates ban expression but reduces diap1 expression. In both cases these transcriptional changes map to small segments of these promoters that recruit Yorkie. Although LC8 complexes with Yap1, a Yorkie homolog, in human cells, an orthologous interaction was not detected in Drosophila cells. Collectively these findings reveal that that Drosophila Ctp is a required regulator of Yorkie-target genes in vivo and suggest that Ctp may interact with a Hippo pathway protein(s) to exert inverse transcriptional effects on Yorkie-target genes.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Animals, Genetically Modified
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Drosophila Proteins / chemistry
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Drosophila Proteins / genetics*
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Drosophila Proteins / metabolism
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Drosophila melanogaster / genetics*
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Drosophila melanogaster / growth & development
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Drosophila melanogaster / metabolism
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Dyneins / chemistry
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Dyneins / genetics*
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Dyneins / metabolism
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Gene Expression Regulation, Developmental*
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Imaginal Discs / growth & development
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Imaginal Discs / metabolism
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Inhibitor of Apoptosis Proteins / genetics
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Inhibitor of Apoptosis Proteins / metabolism
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Intracellular Signaling Peptides and Proteins / genetics*
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Intracellular Signaling Peptides and Proteins / metabolism
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MicroRNAs / genetics
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MicroRNAs / metabolism
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Microscopy, Confocal
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism
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Protein Multimerization
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Protein Serine-Threonine Kinases / genetics*
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Protein Serine-Threonine Kinases / metabolism
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RNA Interference
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Signal Transduction / genetics*
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Trans-Activators / genetics
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Trans-Activators / metabolism
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Wings, Animal / growth & development
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Wings, Animal / metabolism
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YAP-Signaling Proteins
Substances
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DIAP1 protein, Drosophila
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Drosophila Proteins
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Inhibitor of Apoptosis Proteins
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Intracellular Signaling Peptides and Proteins
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MicroRNAs
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Nuclear Proteins
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Trans-Activators
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YAP-Signaling Proteins
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Yki protein, Drosophila
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bantam microRNA, Drosophila
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ctp protein, Drosophila
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Protein Serine-Threonine Kinases
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hpo protein, Drosophila
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Dyneins