title: DRE-1/FBXO11-dependent degradation of BLMP-1/BLIMP-1 governs C. elegans developmental timing and maturation.
abstract: Developmental timing genes catalyze stem cell progression and animal maturation programs across taxa. Caenorhabditis elegans DRE-1/FBXO11 functions in an SCF E3-ubiquitin ligase complex to regulate the transition to adult programs, but its cognate proteolytic substrates are unknown. Here, we identify the conserved transcription factor BLMP-1 as a substrate of the SCF(DRE-1/FBXO11) complex. blmp-1 deletion suppressed dre-1 mutant phenotypes and exhibited developmental timing defects opposite to dre-1. blmp-1 also opposed dre-1 for other life history traits, including entry into the dauer diapause and longevity. BLMP-1 protein was strikingly elevated upon dre-1 depletion and dysregulated in a stage- and tissue-specific manner. The role of DRE-1 in regulating BLMP-1 stability is evolutionary conserved, as we observed direct protein interaction and degradation function for worm and human counterparts. Taken together, posttranslational regulation of BLMP-1/BLIMP-1 by DRE-1/FBXO11 coordinates C. elegans developmental timing and other life history traits, suggesting that this two-protein module mediates metazoan maturation processes.
authors.affiliation: Max Planck Institute for Biology of Ageing, Joseph-Stelzmann-Straße 9b, 50931 Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD), University of Cologne, 50674 Cologne, Germany.
authors.forename: Moritz
authors.initials: M
authors.lastname: Horn
authors.affiliation: Max Planck Institute for Biology of Ageing, Joseph-Stelzmann-Straße 9b, 50931 Cologne, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Geisen
authors.affiliation: Department of Pathology, NYU Cancer Institute, New York University School of Medicine, 522 First Avenue, SRB 1107, New York, NY 10016, USA; Howard Hughes Medical Institute, Department of Pathology, NYU Cancer Institute, New York University School of Medicine, 522 First Avenue, SRB 1107, New York, NY 10016, USA.
authors.forename: Lukas
authors.initials: L
authors.lastname: Cermak
authors.affiliation: Max Planck Institute for Biology of Ageing, Joseph-Stelzmann-Straße 9b, 50931 Cologne, Germany.
authors.forename: Ben
authors.initials: B
authors.lastname: Becker
authors.affiliation: Max Planck Institute for Biology of Ageing, Joseph-Stelzmann-Straße 9b, 50931 Cologne, Germany.
authors.forename: Shuhei
authors.initials: S
authors.lastname: Nakamura
authors.affiliation: Max Planck Institute for Biology of Ageing, Joseph-Stelzmann-Straße 9b, 50931 Cologne, Germany.
authors.forename: Corinna
authors.initials: C
authors.lastname: Klein
authors.affiliation: Department of Pathology, NYU Cancer Institute, New York University School of Medicine, 522 First Avenue, SRB 1107, New York, NY 10016, USA; Howard Hughes Medical Institute, Department of Pathology, NYU Cancer Institute, New York University School of Medicine, 522 First Avenue, SRB 1107, New York, NY 10016, USA.
authors.forename: Michele
authors.initials: M
authors.lastname: Pagano
authors.affiliation: Max Planck Institute for Biology of Ageing, Joseph-Stelzmann-Straße 9b, 50931 Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD), University of Cologne, 50674 Cologne, Germany; Department of Molecular and Cellular Biology, Huffington Center on Aging, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: aantebi@age.mpg.de.
authors.forename: Adam
authors.initials: A
authors.lastname: Antebi
mesh_terms: D000818:Animals; D015153:Blotting, Western; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism; D044783:F-Box Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D020868:Gene Silencing; D006066:Gonads / Q000166:cytology / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007124:Immunoenzyme Techniques; D007814:Larva / Q000166:cytology* / Q000378:metabolism; D008136:Longevity / Q000235:genetics*; D009928:Organ Specificity; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D059748:Proteolysis; D034741:RNA, Small Interfering / Q000235:genetics; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D054875:Ubiquitination
chemical_list: D029742:Caenorhabditis elegans Proteins; C519094:DRE-1 protein, C elegans; D044783:F-Box Proteins; D034741:RNA, Small Interfering; D014157:Transcription Factors; D046988:Proteasome Endopeptidase Complex