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| Home > Publications Database > Ohgata, the Single Drosophila Ortholog of Human Cereblon, Regulates Insulin Signaling-dependent Organismic Growth. |
| Home > Publications Database > Ohgata, the Single Drosophila Ortholog of Human Cereblon, Regulates Insulin Signaling-dependent Organismic Growth. |
| Journal Article | DZNE-2020-05222 |
; ; ; ; ;
2016
Soc.60645
Bethesda, Md.
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Please use a persistent id in citations: doi:10.1074/jbc.M116.757823
Abstract: Cereblon (CRBN) is a substrate receptor of the E3 ubiquitin ligase complex that is highly conserved in animals and plants. CRBN proteins have been implicated in various biological processes such as development, metabolism, learning, and memory formation, and their impairment has been linked to autosomal recessive non-syndromic intellectual disability and cancer. Furthermore, human CRBN was identified as the primary target of thalidomide teratogenicity. Data on functional analysis of CRBN family members in vivo, however, are still scarce. Here we identify Ohgata (OHGT), the Drosophila ortholog of CRBN, as a regulator of insulin signaling-mediated growth. Using ohgt mutants that we generated by targeted mutagenesis, we show that its loss results in increased body weight and organ size without changes of the body proportions. We demonstrate that ohgt knockdown in the fat body, an organ analogous to mammalian liver and adipose tissue, phenocopies the growth phenotypes. We further show that overgrowth is due to an elevation of insulin signaling in ohgt mutants and to the down-regulation of inhibitory cofactors of circulating Drosophila insulin-like peptides (DILPs), named acid-labile subunit and imaginal morphogenesis protein-late 2. The two inhibitory proteins were previously shown to be components of a heterotrimeric complex with growth-promoting DILP2 and DILP5. Our study reveals OHGT as a novel regulator of insulin-dependent organismic growth in Drosophila.
Keyword(s): Adaptor Proteins, Signal Transducing (MeSH) ; Animals (MeSH) ; Cell Line (MeSH) ; Drosophila Proteins: genetics (MeSH) ; Drosophila Proteins: metabolism (MeSH) ; Drosophila melanogaster (MeSH) ; Gene Knockdown Techniques (MeSH) ; Humans (MeSH) ; Insulins: genetics (MeSH) ; Insulins: metabolism (MeSH) ; Peptide Hydrolases: genetics (MeSH) ; Peptide Hydrolases: metabolism (MeSH) ; Signal Transduction: physiology (MeSH) ; Ubiquitin-Protein Ligases (MeSH) ; CRBN protein, human ; Drosophila Proteins ; Ilp5 protein, Drosophila ; Insulins ; Peptide Hydrolases
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