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THE ROLE OF DROSOPHILA SUMO CONJUGATING ENZYME LESSWRIGHT IN LARVAL HEMATOPOIESIS: EFFECTS ON CACTUS, DORSAL AND DORSAL-RELATED IMMUNITY FACTOR (DIF)

Abraham, Jinu
http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1187275172

Abstract Details

2007, Doctor of Philosophy (PhD), Ohio University, Molecular and Cellular Biology (Arts and Sciences).
Hemocytes (blood cells) play an important role in cellular immune response and development in Drosophila. The evolutionarily conserved Toll (Tl) signaling pathway is one of the important pathways which regulate Drosophila hematopoiesis. This study focuses on how larval hematopoiesis is regulated by the interactions between the Toll pathway and a UBC9 family SUMO conjugase called Lesswright (Lwr). My results have revealed at least three layers of interactions between Lwr and the Tl signaling pathway. Firstly, Lwr interacts with and stabilizes Cactus (Cact), an inhibitor of Tl signaling, by preventing the phosphorylation of Cact. Accordingly, lwr mutant larvae show abnormal proliferation and differentiation of hemocytes. Loss-of-function mutations in cact also cause a very high increase in hemocyte number. Interestingly the lwr cact double mutant larvae not only showed a reduced number of hemocytes but also had a very high percentage of lamellocytes which is contrary to the phenotype observed in lwr and cact single mutants. Since Dorsal (Dl) and Dorsal-related immunity factor (Dif), the transcription factors of Tl signaling pathway, would be present in the unSUMOylated state in the lwr cact double mutants, the unSUMOylated form of these transcription factors might be responsible for triggering the abnormal differentiation of lamellocytes and a reduction in the total hemocyte count. The second layer of regulation involves the SUMOylation of Dl by Lwr. SUMOylated Dl was found to be more potent than unSUMOylated Dl in terms of hemocyte proliferation and differentiation. I also found that SUMOylation regulates of the transcriptional activity of Dl in a promoter dependent manner. The third layer of regulation involves Lwr and the transcription factor Dif. My results have demonstrated that Dif is also SUMO conjugated by Lwr. Interestingly, SUMOylation of Dif reduces the potency of Dif in terms of blood cell proliferation and differentiation. These data show that SUMOylation has opposite effects on Dl and Dif in Drosophila hematopoiesis. However, the SUMOylation of Dl and Dif does not completely explain the reduction in the total hemocyte count and the drastic increase in the number of lamellocytes in the lwr cact double mutants, indicating a more complex mode of regulation of larval hematopoiesis by Lwr. The overexpression of Drosophila p53 (Dmp53) in the differentiated hemocytes caused an increase in the total hemocyte count. But when Dmp53 was overexpressed in the lwr mutant background the hemocyte count was drastically reduced, indicating that the SUMOylation status of Dmp53 might affect its activity in hematopoiesis. Interestingly, when Dmp53 was overexpressed in the undifferentiated prohemocytes, a decrease in the total hemocyte count compared to the control was observed suggesting that Dmp53 may have a cell type-specific role in larval hematopoiesis. Thus, my studies show the complex regulatory role of Lwr and suggest a novel role for Dmp53 in Drosophila larval hematopoiesis.
Soichi Tanda (Advisor)
154 p.
Drosophila hematopoiesis; SUMO conjugatng enzyme; Lesswright; Cactus; Dorsal and DIF; Dif; Toll signaling pathway; Plasmatocytes; Lamellocytes

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Citations

  • Abraham, J. (2007). THE ROLE OF DROSOPHILA SUMO CONJUGATING ENZYME LESSWRIGHT IN LARVAL HEMATOPOIESIS: EFFECTS ON CACTUS, DORSAL AND DORSAL-RELATED IMMUNITY FACTOR (DIF) [Doctoral dissertation, Ohio University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1187275172

    APA Style (7th edition)

  • Abraham, Jinu. THE ROLE OF DROSOPHILA SUMO CONJUGATING ENZYME LESSWRIGHT IN LARVAL HEMATOPOIESIS: EFFECTS ON CACTUS, DORSAL AND DORSAL-RELATED IMMUNITY FACTOR (DIF). 2007. Ohio University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1187275172.

    MLA Style (8th edition)

  • Abraham, Jinu. "THE ROLE OF DROSOPHILA SUMO CONJUGATING ENZYME LESSWRIGHT IN LARVAL HEMATOPOIESIS: EFFECTS ON CACTUS, DORSAL AND DORSAL-RELATED IMMUNITY FACTOR (DIF)." Doctoral dissertation, Ohio University, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1187275172

    Chicago Manual of Style (17th edition)

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This open access ETD is published by Ohio University and OhioLINK.