Caenorhabditis elegans lin-35/Rb, efl-1/E2F and other synthetic multivulva genes negatively regulate the anaphase-promoting complex gene mat-3/APC8

Genetics. 2004 Jun;167(2):663-72. doi: 10.1534/genetics.103.026021.

Abstract

Retinoblastoma (Rb)/E2F complexes repress expression of many genes important for G(1)-to-S transition, but also appear to regulate gene expression at other stages of the cell cycle. In C. elegans, lin-35/Rb and other synthetic Multivulva (SynMuv) group B genes function redundantly with other sets of genes to regulate G(1)/S progression, vulval and pharyngeal differentiation, and other unknown processes required for viability. Here we show that lin-35/Rb, efl-1/E2F, and other SynMuv B genes negatively regulate a component of the anaphase-promoting complex or cyclosome (APC/C). The APC/C is a multisubunit complex that promotes metaphase-to-anaphase progression and G(1) arrest by targeting different substrates for ubiquitination and proteasome-mediated destruction. The C. elegans APC/C gene mat-3/APC8 has been defined by temperature-sensitive embryonic lethal alleles that strongly affect germline meiosis and mitosis but only weakly affect somatic development. We describe severe nonconditional mat-3 alleles and a hypomorphic viable allele (ku233), all of which affect postembryonic cell divisions including those of the vulval lineage. The ku233 lesion is located outside of the mat-3 coding region and reduces mat-3 mRNA expression. Loss-of-function alleles of lin-35/Rb and other SynMuv B genes suppress mat-3(ku233) defects by restoring mat-3 mRNA to wild-type levels. Therefore, Rb/E2F complexes appear to repress mat-3 expression.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anaphase-Promoting Complex-Cyclosome
  • Animals
  • Base Sequence
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans Proteins / genetics*
  • Cell Cycle Proteins / genetics*
  • Cell Differentiation
  • DNA Primers
  • DNA-Binding Proteins / genetics*
  • E2F Transcription Factors
  • Epidermal Growth Factor / genetics*
  • Female
  • Gene Expression Regulation
  • Genes, Retinoblastoma
  • Genes, Synthetic
  • Pharynx / cytology
  • Pharynx / growth & development
  • Transcription Factors / genetics*
  • Ubiquitin-Protein Ligase Complexes / deficiency
  • Ubiquitin-Protein Ligase Complexes / genetics*
  • Vulva / cytology
  • Vulva / growth & development

Substances

  • Caenorhabditis elegans Proteins
  • Cell Cycle Proteins
  • DNA Primers
  • DNA-Binding Proteins
  • E2F Transcription Factors
  • Transcription Factors
  • efl-1 protein, C elegans
  • Lin-3 protein, C elegans
  • Epidermal Growth Factor
  • Ubiquitin-Protein Ligase Complexes
  • Anaphase-Promoting Complex-Cyclosome