Caenorhabditis elegans lin-35/Rb, efl-1/E2F and other synthetic multivulva genes negatively regulate the anaphase-promoting complex gene mat-3/APC8.
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.
Garbe
David
D
Department of Genetics, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6100, USA.
Doto
Jeffrey B
JB
Sundaram
Meera V
MV
D064173:Anaphase-Promoting Complex-Cyclosome; D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics*; D002454:Cell Differentiation; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics*; D050684:E2F Transcription Factors; D004815:Epidermal Growth Factor / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D016161:Genes, Retinoblastoma; D005813:Genes, Synthetic; D010614:Pharynx / Q000166:cytology / Q000254:growth & development; D014157:Transcription Factors / Q000235:genetics*; D043743:Ubiquitin-Protein Ligase Complexes / Q000172:deficiency / Q000235:genetics*; D014844:Vulva / Q000166:cytology / Q000254:growth & development
D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D014157:Transcription Factors; C493765:efl-1 protein, C elegans; C075912:Lin-3 protein, C elegans; D004815:Epidermal Growth Factor; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome