DRE-1/FBXO11-Dependent Degradation of BLMP-1/BLIMP-1 Governs C. elegans Developmental Timing and Maturation

• Published in: Developmental cell 2014-03, Vol.28 (6), p.697-710
• Main Authors: Horn, Moritz, Geisen, Christoph, Cermak, Lukas, Becker, Ben, Nakamura, Shuhei, Klein, Corinna, Pagano, Michele, Antebi, Adam
• Format: Article
• Language: English
• Subjects: Animals; Blotting, Western; Caenorhabditis elegans - genetics; Caenorhabditis elegans - growth & development; Caenorhabditis elegans - metabolism; Caenorhabditis elegans Proteins - antagonists & inhibitors; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Cell Differentiation; Epidermis - cytology; Epidermis - metabolism; F-Box Proteins - antagonists & inhibitors; F-Box Proteins - genetics; F-Box Proteins - metabolism; Gene Expression Regulation, Developmental; Gene Silencing; Gonads - cytology; Gonads - metabolism; HEK293 Cells; Humans; Immunoenzyme Techniques; Larva - cytology; Larva - metabolism; Longevity - genetics; Organ Specificity; Proteasome Endopeptidase Complex - metabolism; Proteolysis; RNA, Small Interfering - genetics; Time Factors; Transcription Factors - genetics; Transcription Factors - metabolism; Ubiquitination
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2014.01.028

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 SCFDRE-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. •The SCFDRE-1 E3-ubiquitin ligase complex targets BLMP-1 as a substrate•blmp-1 is a heterochronic gene controlling epidermal and gonadal maturation•The BLMP-1/DRE-1 module controls C. elegans dauer formation, molting, and longevity•Human FBXO11 degrades human BLIMP-1, showing a conserved relationship C. elegans DRE-1/FBXO11 functions in a SCF E3-ubiquitin ligase complex to regulate developmental timing. Horn et al. identify the conserved transcription factor BLMP-1 as a SCFDRE-1/FBXO11 substrate regulating C. elegans maturation. DRE-1 degradation of BLMP-1 is conserved in mammals, suggesting that the FBXO11/BLIMP-1 module might coordinate metazoan maturation processes.