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@ARTICLE{Wakabayashi:138900,
author = {Wakabayashi, Satoru and Sawamura, Naoya and Voelzmann,
André and Brömer, Meike and Asahi, Toru and Hoch, Michael},
title = {{O}hgata, the {S}ingle {D}rosophila {O}rtholog of {H}uman
{C}ereblon, {R}egulates {I}nsulin {S}ignaling-dependent
{O}rganismic {G}rowth.},
journal = {The journal of biological chemistry},
volume = {291},
number = {48},
issn = {0021-9258},
address = {Bethesda, Md.},
publisher = {Soc.60645},
reportid = {DZNE-2020-05222},
pages = {25120-25132},
year = {2016},
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.},
keywords = {Adaptor Proteins, Signal Transducing / Animals / Cell Line
/ Drosophila Proteins: genetics / Drosophila Proteins:
metabolism / Drosophila melanogaster / Gene Knockdown
Techniques / Humans / Insulins: genetics / Insulins:
metabolism / Peptide Hydrolases: genetics / Peptide
Hydrolases: metabolism / Signal Transduction: physiology /
Ubiquitin-Protein Ligases / CRBN protein, human (NLM
Chemicals) / Drosophila Proteins (NLM Chemicals) / Ilp5
protein, Drosophila (NLM Chemicals) / Insulins (NLM
Chemicals) / Peptide Hydrolases (NLM Chemicals)},
cin = {AG Brömer 1},
ddc = {540},
cid = {I:(DE-2719)5000021},
pnm = {341 - Molecular Signaling (POF3-341)},
pid = {G:(DE-HGF)POF3-341},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:27702999},
pmc = {pmc:PMC5122779},
doi = {10.1074/jbc.M116.757823},
url = {https://pub.dzne.de/record/138900},
}