Roles of C/EBP class bZip proteins in the growth and cell competition of <i>Rp</i> ('Minute') mutants in <i>Drosophila</i>.

Abstract

Reduced copy number of ribosomal protein (<i>Rp</i>) genes adversely affects both flies and mammals. <i>Xrp1</i> encodes a reportedly <i>Drosophila</i>-specific AT-hook, bZIP protein responsible for many of the effects including the elimination of <i>Rp</i> mutant cells by competition with wild type cells. Irbp18, an evolutionarily conserved bZIP gene, heterodimerizes with Xrp1 and with another bZip protein, dATF4. We show that Irbp18 is required for the effects of Xrp1, whereas dATF4 does not share the same phenotype, indicating that Xrp1/Irbp18 is the complex active in <i>Rp</i> mutant cells, independently of other complexes that share Irbp18. Xrp1 and Irbp18 transcripts and proteins are upregulated in <i>Rp</i> mutant cells by auto-regulatory expression that depends on the Xrp1 DNA binding domains and is necessary for cell competition. We show that Xrp1 is conserved beyond <i>Drosophila</i>, although under positive selection for rapid evolution, and that at least one human bZip protein can similarly affect <i>Drosophila</i> development.