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Free keywords:
Animals
Blotting, Western
Caenorhabditis elegans/genetics/*growth & development/metabolism
Caenorhabditis elegans Proteins/antagonists & inhibitors/genetics/*metabolism
Cell Differentiation
Epidermis/cytology/metabolism
F-Box Proteins/antagonists & inhibitors/genetics/*metabolism
*Gene Expression Regulation, Developmental
Gene Silencing
Gonads/cytology/metabolism
HEK293 Cells
Humans
Immunoenzyme Techniques
Larva/*cytology/metabolism
Longevity/*genetics
Organ Specificity
Proteasome Endopeptidase Complex/metabolism
Proteolysis
RNA, Small Interfering/genetics
Time Factors
Transcription Factors/genetics/metabolism
Ubiquitination
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.
