Drosophila oogenesis is especially well suited for studying stem cell biology, cellular differentiation, and morphogenesis. The small modifier protein ubiquitin regulates many cellular pathways. Ubiquitin is conjugated to target proteins by a diverse class of enzymes called ubiquitin E3 ligases. Here we characterize the requirement of Cul-5, a key component of a subgroup of Cullin-RING-type ubiquitin E3 ligases, in Drosophila oogenesis. We find that reduced cul-5 activity causes the formation of aberrant follicles that are characterized by excess germ cells. We show that germ line cells overproliferate in cul-5 mutant females, causing the formation of abnormally large germ line cysts. Also, the follicular epithelium that normally encapsulates single germ line cysts develops aberrantly in cul-5 mutant, leading to defects in cyst formation. We additionally found that Cul-5 is required for germ cell maintenance, as germ cells are depleted in a substantial fraction of cul-5 mutant ovaries. All of these cul-5 phenotypes are strongly enhanced by reduced activity of gustavus (gus), which encodes a substrate receptor of Cul-5-based ubiquitin E3 ligases. Taken together, our results implicate Cul-5/Gus ubiquitin E3 ligases in ovarian tissue morphogenesis, germ cell proliferation and maintenance of the ovarian germ cell population.

It has been recently reported that p53 activation can lead to the induction of PKR-eIF2alpha phosphorylation pathway. However, we demonstrate that PKR and eIF2alpha phosphorylation at serine 51 are not downstream of p53 in response to doxorubicin treatment suggesting that PKR is not a universal target of p53 as proposed.

it has been recently reported that p53 activation can lead to the induction of PKR-eIF2 alpha phosphorylation pathway. however, we demonstrate that PKR3 and eIF2 alpha phosphorylation at serine 51 are not downstream of p53 in response to doxorubicin treatment suggesting that PKR is not a universal target of p53 as proposed.