138900 20240321220522.0 10.1074/jbc.M116.757823 doi pmid:27702999 pmid pmc:PMC5122779 pmc 0021-9258 ISSN 1067-8816 ISSN 1083-351X ISSN altmetric:12468371 altmetric DZNE-2020-05222 English 540 Wakabayashi, Satoru P:(DE-HGF)0 0 Ohgata, the Single Drosophila Ortholog of Human Cereblon, Regulates Insulin Signaling-dependent Organismic Growth. Bethesda, Md. 2016 Soc.60645 online Crossref American Society for Biochemistry & Molecular Biology (ASBMB) 2016-10-04 print Crossref American Society for Biochemistry & Molecular Biology (ASBMB) 2016-11-25 article DRIVER Output Types/Journal article DataCite Journal Article journal journal PUB:(DE-HGF)16 1585917942_16157 PUB:(DE-HGF) ARTICLE BibTeX JOURNAL_ARTICLE ORCID Journal Article 0 EndNote 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. 341 - Molecular Signaling (POF3-341) G:(DE-HGF)POF3-341 POF3-341 POF III 0 Dataset connected to CrossRef, PubMed, CRBN protein, human NLM Chemicals Drosophila Proteins NLM Chemicals Ilp5 protein, Drosophila NLM Chemicals Insulins NLM Chemicals Peptide Hydrolases EC 3.4.- NLM Chemicals 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 Sawamura, Naoya P:(DE-HGF)0 1 Corresponding author Voelzmann, André P:(DE-HGF)0 2 Brömer, Meike P:(DE-2719)2810307 3 dzne Asahi, Toru P:(DE-HGF)0 4 Hoch, Michael P:(DE-HGF)0 5 10.1074/jbc.m116.757823 : American Society for Biochemistry & Molecular Biology (ASBMB), 2016-10-04 48 25120-25132 journal-article Crossref Journal of Biological Chemistry 291 2016 0021-9258 10.1074/jbc.M116.757823 Vol. 291, no. 48, p. 25120 - 25132 PERI:(DE-600)1474604-9 48 291:48<25120 - 25132 25120-25132 The journal of biological chemistry 291 2016 0021-9258 Pubmed Central http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5122779 oai:pub.dzne.de:138900 VDB Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 3 P:(DE-2719)2810307 DE-HGF Forschungsbereich Gesundheit Erkrankungen des Nervensystems G:(DE-HGF)POF3-340 G:(DE-HGF)POF3-341 G:(DE-HGF)POF3-300 Molecular Signaling 0 2016 DBCoverage StatID:(DE-HGF)0200 StatID SCOPUS DBCoverage StatID:(DE-HGF)0300 StatID Medline DBCoverage StatID:(DE-HGF)0310 StatID NCBI Molecular Biology Database DBCoverage StatID:(DE-HGF)0320 StatID PubMed Central JCR StatID:(DE-HGF)0100 StatID J BIOL CHEM : 2017 DBCoverage StatID:(DE-HGF)0600 StatID Ebsco Academic Search Peer Review StatID:(DE-HGF)0030 StatID ASC DBCoverage StatID:(DE-HGF)0199 StatID Clarivate Analytics Master Journal List WoS StatID:(DE-HGF)0110 StatID Science Citation Index DBCoverage StatID:(DE-HGF)0150 StatID Web of Science Core Collection WoS StatID:(DE-HGF)0111 StatID Science Citation Index Expanded DBCoverage StatID:(DE-HGF)1030 StatID Current Contents - Life Sciences DBCoverage StatID:(DE-HGF)1050 StatID BIOSIS Previews IF < 5 StatID:(DE-HGF)9900 StatID I:(DE-2719)5000021 AG Brömer 1 Ubiquitin-mediated Processes in Neurodegenerative Diseases 0 journal VDB I:(DE-2719)5000021 UNRESTRICTED 10.1016/S1043-2760(01)00548-3 -- missing cx lookup -- Crossref 10.1016/S1043-2760(01)00548-3 10.1038/nrg1989 -- missing cx lookup -- Crossref 10.1038/nrg1989 10.1016/S0960-9822(01)00068-9 -- missing cx lookup -- Crossref 10.1016/S0960-9822(01)00068-9 10.1038/nature05412 -- missing cx lookup -- Crossref 10.1038/nature05412 10.1016/S0960-9822(02)01043-6 -- missing cx lookup -- Crossref 10.1016/S0960-9822(02)01043-6 10.1126/science.1070058 -- missing cx lookup -- Crossref 10.1126/science.1070058 10.1016/S0092-8674(03)00713-X -- missing cx lookup -- Crossref 10.1016/S0092-8674(03)00713-X 10.1016/j.cmet.2009.08.002 -- missing cx lookup -- Crossref 10.1016/j.cmet.2009.08.002 10.1016/j.cell.2012.08.019 -- missing cx lookup -- Crossref 10.1016/j.cell.2012.08.019 10.1371/journal.pgen.1005481 -- missing cx lookup -- Crossref 10.1371/journal.pgen.1005481 10.1371/journal.pbio.1002392 -- missing cx lookup -- Crossref 10.1371/journal.pbio.1002392 10.1016/j.cmet.2016.03.003 -- missing cx lookup -- Crossref 10.1016/j.cmet.2016.03.003 10.1016/j.cmet.2008.02.003 -- missing cx lookup -- Crossref 10.1016/j.cmet.2008.02.003 10.1186/jbiol72 -- missing cx lookup -- Crossref 10.1186/jbiol72 10.1016/j.devcel.2009.10.008 -- missing cx lookup -- Crossref 10.1016/j.devcel.2009.10.008 10.1016/j.devcel.2009.10.009 -- missing cx lookup -- Crossref 10.1016/j.devcel.2009.10.009 10.1212/01.WNL.0000146196.01316.A2 -- missing cx lookup -- Crossref 10.1212/01.WNL.0000146196.01316.A2 10.1126/science.1177319 -- missing cx lookup -- Crossref 10.1126/science.1177319 10.2337/db12-1030 -- missing cx lookup -- Crossref 10.2337/db12-1030 10.1016/j.bbrc.2015.07.068 -- missing cx lookup -- Crossref 10.1016/j.bbrc.2015.07.068 10.1038/srep29986 -- missing cx lookup -- Crossref 10.1038/srep29986 10.1038/leu.2012.119 -- missing cx lookup -- Crossref 10.1038/leu.2012.119 10.1126/science.1244851 -- missing cx lookup -- Crossref 10.1126/science.1244851 10.1126/science.1244917 -- missing cx lookup -- Crossref 10.1126/science.1244917 10.1038/nm.4128 -- missing cx lookup -- Crossref 10.1038/nm.4128 10.1007/s00424-016-1854-1 -- missing cx lookup -- Crossref 10.1007/s00424-016-1854-1 10.1038/nature05175 -- missing cx lookup -- Crossref 10.1038/nature05175 10.1182/blood-2011-05-356063 -- missing cx lookup -- Crossref 10.1182/blood-2011-05-356063 10.1038/nature13527 -- missing cx lookup -- Crossref 10.1038/nature13527 10.1038/nature14610 -- missing cx lookup -- Crossref 10.1038/nature14610 10.1038/nature18611 -- missing cx lookup -- Crossref 10.1038/nature18611 10.1016/j.bbrc.2016.06.091 -- missing cx lookup -- Crossref 10.1016/j.bbrc.2016.06.091 10.1016/j.molcel.2016.02.032 -- missing cx lookup -- Crossref 10.1016/j.molcel.2016.02.032 10.1016/j.bbamcr.2011.01.005 -- missing cx lookup -- Crossref 10.1016/j.bbamcr.2011.01.005 1997 Crossref Pignoni 1997 10.1534/genetics.113.160713 -- missing cx lookup -- Crossref 10.1534/genetics.113.160713 10.1016/j.celrep.2013.06.020 -- missing cx lookup -- Crossref 10.1016/j.celrep.2013.06.020 10.1101/gad.249763.114 -- missing cx lookup -- Crossref 10.1101/gad.249763.114 10.1371/journal.pone.0097332 -- missing cx lookup -- Crossref 10.1371/journal.pone.0097332 10.1242/jcs.120964 -- missing cx lookup -- Crossref 10.1242/jcs.120964 10.1038/nature08698 -- missing cx lookup -- Crossref 10.1038/nature08698 10.1080/15419060600631839 -- missing cx lookup -- Crossref 10.1080/15419060600631839 10.1016/j.devcel.2015.02.012 -- missing cx lookup -- Crossref 10.1016/j.devcel.2015.02.012 10.1093/nar/gku340 -- missing cx lookup -- Crossref 10.1093/nar/gku340 10.1002/jcc.20084 -- missing cx lookup -- Crossref 10.1002/jcc.20084 10.1093/bioinformatics/btg180 -- missing cx lookup -- Crossref 10.1093/bioinformatics/btg180 10.1093/bioinformatics/17.8.754 -- missing cx lookup -- Crossref 10.1093/bioinformatics/17.8.754 10.1093/bioinformatics/btg427 -- missing cx lookup -- Crossref 10.1093/bioinformatics/btg427 10.1093/nar/gks1067 -- missing cx lookup -- Crossref 10.1093/nar/gks1067 10.1093/nar/gkl124 -- missing cx lookup -- Crossref 10.1093/nar/gkl124 10.1080/07391102.2014.968875 -- missing cx lookup -- Crossref 10.1080/07391102.2014.968875 10.1371/journal.pone.0023505 -- missing cx lookup -- Crossref 10.1371/journal.pone.0023505 10.1093/nar/gku383 -- missing cx lookup -- Crossref 10.1093/nar/gku383 10.1002/pmic.200800646 -- missing cx lookup -- Crossref 10.1002/pmic.200800646 10.1093/bioinformatics/btm066 -- missing cx lookup -- Crossref 10.1093/bioinformatics/btm066 10.1093/nar/gkv1046 -- missing cx lookup -- Crossref 10.1093/nar/gkv1046 10.1016/j.cell.2014.05.010 -- missing cx lookup -- Crossref 10.1016/j.cell.2014.05.010 10.1042/BJ20091181 -- missing cx lookup -- Crossref 10.1042/BJ20091181 10.1016/S0092-8674(00)80595-4 -- missing cx lookup -- Crossref 10.1016/S0092-8674(00)80595-4 10.1101/gad.1098703 -- missing cx lookup -- Crossref 10.1101/gad.1098703 10.1038/70293 -- missing cx lookup -- Crossref 10.1038/70293 10.1038/sj.onc.1203739 -- missing cx lookup -- Crossref 10.1038/sj.onc.1203739 1993 Crossref Garbe 1993 10.1038/nsmb.2874 -- missing cx lookup -- Crossref 10.1038/nsmb.2874 10.1093/jb/mvj006 -- missing cx lookup -- Crossref 10.1093/jb/mvj006 10.1534/genetics.103.025965 -- missing cx lookup -- Crossref 10.1534/genetics.103.025965 10.1677/joe.0.1700063 -- missing cx lookup -- Crossref 10.1677/joe.0.1700063 10.1073/pnas.1502166113 -- missing cx lookup -- Crossref 10.1073/pnas.1502166113 10.1111/j.1471-4159.2005.03344.x -- missing cx lookup -- Crossref 10.1111/j.1471-4159.2005.03344.x 10.1038/ncomms4924 -- missing cx lookup -- Crossref 10.1038/ncomms4924 10.1038/srep10667 -- missing cx lookup -- Crossref 10.1038/srep10667 10.1101/gad.1624008 -- missing cx lookup -- Crossref 10.1101/gad.1624008 10.1073/pnas.0406789102 -- missing cx lookup -- Crossref 10.1073/pnas.0406789102