Activator protein 1 (AP-1) constitutes an important family of basic region leucine zipper (bZIP) transcription factors. The AP-1 proteins, consisting of Fos, Jun, ATF2 and Maf subfamilies, regulate a variety of cellular processes, including cellular proliferation, differentiation and death, and stress responses. They function as homodimers or heterodimers and bind AP-1 consensus sequences in the promoter regions of various target genes to regulate transcription. Despite the fact that these proteins function as dimers, genetic analyses of individual genes in mice and Drosophila have not revealed overlapping phenotypes, most likely attributed to compensation of one AP-1 protein for another. To overcome these limitations, we are applying genetic and biochemical approaches, along with our bimolecular fluorescence complementation (BiFC) assay, to functionally analyze the role of AP-1 dimers in C. elegans. Using phylogenetic and biochemical analyses, we have identified C. elegans
fos-1 and
jun-1, encoded by F29G9.4 and T24H10.7, respectively. Knockdown of
fos-1 or
jun-1 by feeding RNA interference (RNAi) resulted in sterility, specifically due to defects in ovulation. Furthermore, genetic analysis has demonstrated that the ovulation defect resulting from
fos-1 RNAi is reduced by a mutation in
ipp-5, a gene encoding inositol 5-phosphatase that converts IP<sub>3</sub> into IP<sub>2</sub>. Given that ovulation in C. elegans is regulated by the IP<sub>3</sub> signaling pathway, our results suggest that C. elegans AP-1 may regulate the transcription of molecules in this pathway. RNAi analysis has revealed that
fos-1 and
jun-1 regulate the expression of
plc-1 in the spermatheca. Furthermore, FOS-1 and JUN-1 bind two putative AP-1 consensus sequences identified in the
plc-1 promoter in vitro. Given that
plc-1 is required for regulation of ovulation, our preliminary results suggest that
fos-1 and
jun-1 may regulate ovulation by controlling the transcription of
plc-1. Further analysis of specific AP-1 dimers responsible for the transcriptional regulation of
plc-1 and identification of other AP-1 target genes are underway.