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. Epub 2014 Mar 6.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • Epidermal Cells
  • 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

Substances

  • Caenorhabditis elegans Proteins
  • DRE-1 protein, C elegans
  • F-Box Proteins
  • RNA, Small Interfering
  • Transcription Factors
  • Proteasome Endopeptidase Complex