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Execution of baculovirus-induced apo...

Lannan, Erica A.

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Execution of baculovirus-induced apoptosis in Drosophila melanogaster requires caspases DrICE, DCP1, and Dronc.

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
正題名/作者:	Execution of baculovirus-induced apoptosis in Drosophila melanogaster requires caspases DrICE, DCP1, and Dronc./
作者:	Lannan, Erica A.
面頁冊數:	211 p.
附註:	Adviser: Paul D. Friesen.
Contained By:	Dissertation Abstracts International68-12B.
標題:	Biology, Cell. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3294199
ISBN:	9780549383123

Execution of baculovirus-induced apoptosis in Drosophila melanogaster requires caspases DrICE, DCP1, and Dronc.
Lannan, Erica A.

Execution of baculovirus-induced apoptosis in Drosophila melanogaster requires caspases DrICE, DCP1, and Dronc. - 211 p.

Adviser: Paul D. Friesen.

Thesis (Ph.D.)--The University of Wisconsin - Madison, 2007.

Apoptosis is a cell suicide pathway used by multicellular organisms to eliminate unwanted or damaged cells. Because pathogenesis of many viruses arises from apoptosis, the pathway through which apoptosis is executed is of great interest for many viral diseases. My thesis research has focused on determining host components activated following virus infection. To that end, I have identified the cellular caspases activated upon baculovirus infection to execute apoptosis in the model system of Drosophila melanogaster . By using RNA silencing I demonstrated that three Drosophila caspases, DrICE, DCP1, and Drone, are required for baculovirus-induced cell death in DL-1 cells. I also established the activation order of these caspases following infection. I determined that initiator caspase Drone is required for baculovirus-induced apoptosis upstream of the effector caspases DrICE and DCP1. Importantly, I also found that DCP1 is required for apoptosis at or upstream of DrICE activation. This work, for the first time, shows the requirement of two distinct effector caspases in virus-induced apoptosis, in which one effector caspase requires another effector caspase for activity.

ISBN: 9780549383123Subjects--Topical Terms:

1017686
Biology, Cell.

Execution of baculovirus-induced apoptosis in Drosophila melanogaster requires caspases DrICE, DCP1, and Dronc.
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245 1 0 $a Execution of baculovirus-induced apoptosis in Drosophila melanogaster requires caspases DrICE, DCP1, and Dronc.
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500 $a Source: Dissertation Abstracts International, Volume: 68-12, Section: B, page: 7796.
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520 $a Apoptosis is a cell suicide pathway used by multicellular organisms to eliminate unwanted or damaged cells. Because pathogenesis of many viruses arises from apoptosis, the pathway through which apoptosis is executed is of great interest for many viral diseases. My thesis research has focused on determining host components activated following virus infection. To that end, I have identified the cellular caspases activated upon baculovirus infection to execute apoptosis in the model system of Drosophila melanogaster . By using RNA silencing I demonstrated that three Drosophila caspases, DrICE, DCP1, and Drone, are required for baculovirus-induced cell death in DL-1 cells. I also established the activation order of these caspases following infection. I determined that initiator caspase Drone is required for baculovirus-induced apoptosis upstream of the effector caspases DrICE and DCP1. Importantly, I also found that DCP1 is required for apoptosis at or upstream of DrICE activation. This work, for the first time, shows the requirement of two distinct effector caspases in virus-induced apoptosis, in which one effector caspase requires another effector caspase for activity.
520 $a Cellular and baculovirus apoptotic inhibitors can block apoptosis at various steps along the apoptotic pathway to elucidate caspase activation events. Activation mechanisms of DrICE, DCP1, and Drone were determined by analyzing caspase cleavage in the presence or absence of viral and cellular apoptotic inhibitors. Upon protein overexpression, DrICE, DCP1, and Drone were all spontaneously cleaved. However, an endogenous caspase was required for DrICE and Drone processing, while overexpressed DCP1 was responsible for cleaving itself. This suggested that proDCP1 has limited activity, a characteristic previously thought unique to initiator caspases. Although baculovirus caspase inhibitor P49 has previously been shown to block effector caspase activation in other insect cell lines, in Drosophila P49 and P35 blocked apoptosis downstream of DrICE and DCP1 activation, suggesting P49 has broader versatility for inhibiting caspases than previously thought. Collectively, my studies, for the first time, have shown the specific role and activation mechanisms of three Drosophila caspases following virus-induced apoptosis. Through these studies I have developed a system that can be used to define host components activated by virus infection.
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