2. Academic Validation
  3. DRE-1/FBXO11-dependent degradation of BLMP-1/BLIMP-1 governs C. elegans developmental timing and maturation

DRE-1/FBXO11-dependent degradation of BLMP-1/BLIMP-1 governs C. elegans developmental timing and maturation

  • Dev Cell. 2014 Mar 31;28(6):697-710. doi: 10.1016/j.devcel.2014.01.028.
Moritz Horn 1,  Christoph Geisen 2,  Lukas Cermak 3,  Ben Becker 2,  Shuhei Nakamura 2,  Corinna Klein 2,  Michele Pagano 3,  Adam Antebi 4
Affiliations

Affiliations

  • 1 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.
  • 2 Max Planck Institute for Biology of Ageing, Joseph-Stelzmann-Straße 9b, 50931 Cologne, Germany.
  • 3 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.
  • 4 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.
PMID: 24613396 DOI: 10.1016/j.devcel.2014.01.028
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.

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