The lesswright mutation activates Rel-related proteins, leading to overproduction of larval hemocytes in Drosophila melanogaster

Abstract

The lesswright (lwr) gene encodes an enzyme that conjugates a small ubiquitin-related modifier (SUMO). Since the conjugation of SUMO occurs in many different proteins, a variety of cellular processes probably require lwr function. Here, we demonstrate that lwr function regulates the production of blood cells (hemocytes) in Drosophila larvae. lwr mutant larvae develop many melanotic tumors in the hemolymph at the third instar stage. The formation of melanotic tumors is due to a large number of circulating hemocytes, which is approximately 10 times higher than those of wild type. This overproduction of hemocytes is attributed to the loss of lwr function primarily in hemocytes and the lymph glands, a hematopoietic organ in Drosophila larvae. High incidences of Dorsal (Dl) protein in the nucleus were observed in lwr mutant hemocytes, and the dl and Dorsal-related immunity factor (Dif) mutations were found to be suppressors of the lwr mutation. Therefore, the lwr mutation leads to the activation of these Rel-related proteins, key transcription factors in hematopoiesis. We also demonstrate that dl and Dif play different roles in hematopoiesis. dl primarily stimulates plasmatocyte production, but Dif controls both plasmatocyte and lamellocyte production.

Smt3 is required forDrosophila melanogastermetamorphosis

“…We analysed the expression pattern of these in the PGs of lwr homozygous mutants that had reached L3 (Chiu et al, 2005;Huang et al, 2005a). Similar to smt3i, in lwr mutant larvae we detected severe alterations in the expression levels of Dib (not shown) and βFtz-f1 (Fig.…”

A differential requirement for SUMOylation in proliferating and non-proliferating cells during Drosophila development

“…The formation of melanotic tumors has also been observed in lwr mutant larvae (Chiu et al, 2005;Huang et al, 2005) ), increased lamellocyte differentiation was observed without an increase in the total number of circulating hemocytes (Chiu et al, 2005). Melanotic tumor formation could still take place in these animals but with lower penetrance.…”

Nuclear factor-kappa B pathways in Drosophila

“…This phenotype suggests that cactus and dorsal are expressed in some tissues that do not express Toll (Minakhina and Steward, in press). Studies of the lesswright gene, which encodes a small ubiquitin-like modifier (SUMO)-adding enzyme, indicate that SUMO addition is required for proper regulation of Dorsal and Dif in hemocytes: namely, loss-of-function lesswright mutations result in constitutively nuclear Dorsal and Dif proteins in hemocytes and the formation of melanotic tumors owing to increased numbers of hemocytes (Huang et al, 2005). Similarly, the Drosophila Ubc9 SUMO-lating gene also appears to repress Dorsal and Dif function in controlling lamelocyte proliferation and drosomycin gene expression (Chiu et al, 2005).…”