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

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Horn,  Moritz
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Molecular Genetics of Ageing, Department Antebi, Max Planck Institute for Biology of Ageing, Max Planck Society;

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Geisen,  Christoph
Molecular Genetics of Ageing, Department Antebi, Max Planck Institute for Biology of Ageing, Max Planck Society;

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Becker,  Ben
Molecular Genetics of Ageing, Department Antebi, Max Planck Institute for Biology of Ageing, Max Planck Society;

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Nakamura,  Shuhei
Molecular Genetics of Ageing, Department Antebi, Max Planck Institute for Biology of Ageing, Max Planck Society;

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Klein,  Corinna
Dieterich – Computational RNA Biology and Ageing, Research Groups, Max Planck Institute for Biology of Ageing, Max Planck Society;

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Antebi,  Adam
Molecular Genetics of Ageing, Department Antebi, Max Planck Institute for Biology of Ageing, Max Planck Society;

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Citation

Horn, M., Geisen, C., Cermak, L., Becker, B., Nakamura, S., Klein, C., et al. (2014). DRE-1/FBXO11-Dependent Degradation of BLMP-1/BLIMP-1 Governs C. elegans Developmental Timing and Maturation. DEVELOPMENTAL CELL, 28(6), 697-710. 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.