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Elucidating the Mechanism by which K...

Chapman, Eric Michael.

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Elucidating the Mechanism by which KRI-1/CCM1 Regulates Apoptosis Cell Non-Autonomously in Caenorhabditis elegans.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Elucidating the Mechanism by which KRI-1/CCM1 Regulates Apoptosis Cell Non-Autonomously in Caenorhabditis elegans./
作者:	Chapman, Eric Michael.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2018,
面頁冊數:	298 p.
附註:	Source: Dissertations Abstracts International, Volume: 80-06, Section: B.
Contained By:	Dissertations Abstracts International80-06B.
標題:	Molecular biology. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10937279
ISBN:	9780438681255

Elucidating the Mechanism by which KRI-1/CCM1 Regulates Apoptosis Cell Non-Autonomously in Caenorhabditis elegans.
Chapman, Eric Michael.

Elucidating the Mechanism by which KRI-1/CCM1 Regulates Apoptosis Cell Non-Autonomously in Caenorhabditis elegans. - Ann Arbor : ProQuest Dissertations & Theses, 2018 - 298 p.

Source: Dissertations Abstracts International, Volume: 80-06, Section: B.

Thesis (Ph.D.)--University of Toronto (Canada), 2018.

This item is not available from ProQuest Dissertations & Theses.

Programmed cell death initiated by genotoxic stress requires signalling from surrounding tissues, yet such mechanisms are poorly understood. The C. elegans germline is a powerful model to study cell non-autonomous regulation of apoptosis, since germ cells die in response to DNA damage, and because this death requires regulatory input from the soma. The scaffold protein KRI-1, a homologue of mammalian KRIT1/CCM1, was identified to promote DNA damage-induced germ cell apoptosis from the somatic tissue by an unknown mechanism. I reveal that KRI-1 is required for proper activation of MPK-1/ERK1 in the germline, and genetically up-regulating MPK-1/ERK1 restores germ cell apoptosis in the absence of KRI-1. To determine how KRI-1 signals cell non-autonomously to communicate with MPK-1/ERK1, I conducted a forward genetic screen and identified an ERK5/MAPK pathway and the KLF-3 transcription factor that function downstream of this scaffold. I have shown that like kri-1, mpk-2/erk-5 is expressed in the intestine, as is klf-3, and that over-activation of MPK-2/ERK-5 in this tissue is anti-apoptotic. Furthermore, I found that KRI-1 interacts with K07A9.3/CCM2 and Y45F10D.10/ICAP1, which are required to regulate germ cell apoptosis. RNA sequencing of wild type, kri-1, and kri-1; mpk-2/erk5 mutants, followed by an RNAi screen, identified that the zinc transporter, zipt-2.3/scl39, has a role in regulating germ cell apoptosis. ZIPT-2.3 is expressed in the intestine, and reduced zipt-2.3 expression in the absence of KRI-1 prevents proper zinc storage. This results in suppressed activation of MPK-1/ERK1 and germ cell apoptosis. Therefore, the KRI-1 scaffold protein ensures proper activation of MPK-1/ERK1 and germ cell apoptosis by regulating zinc storage.

ISBN: 9780438681255Subjects--Topical Terms:

517296
Molecular biology.
Subjects--Index Terms:

Apoptosis

Elucidating the Mechanism by which KRI-1/CCM1 Regulates Apoptosis Cell Non-Autonomously in Caenorhabditis elegans.
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