DC Field | Value | Language |
---|---|---|
dc.contributor.advisor | Lim, Dae-Sik | - |
dc.contributor.advisor | 임대식 | - |
dc.contributor.author | Oh, Sang-Phil | - |
dc.contributor.author | 오상필 | - |
dc.date.accessioned | 2011-12-12T07:56:04Z | - |
dc.date.available | 2011-12-12T07:56:04Z | - |
dc.date.issued | 2010 | - |
dc.identifier.uri | http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=418771&flag=dissertation | - |
dc.identifier.uri | http://hdl.handle.net/10203/27696 | - |
dc.description | 학위논문(박사) - 한국과학기술원 : 생명과학과, 2010.2, [ viii, 106 p. ] | - |
dc.description.abstract | The Ste-20 family kinase Hippo restricts cell proliferation and promotes apoptosis for proper organ development in $\It{Drosophila}$. In $\It{C. elegans}$, Hippo homolog also regulates longevity. The mammalian Ste20-like protein kinase, MST1 and closely related ortholog MST2, play a role in apoptosis induced by various types of apoptotic stress. MST1 also regulates peripheral naive T cell trafficking and proliferation in mice. However, their functions in mammals are not fully understood. Here, I showed that the MST1-FoxO signaling pathway plays a crucial role in survival, but not apoptosis, of naive T cells. In $\It{Mst1^{-/-}}$ mice, peripheral T cells showed impaired FoxO1/3 activation and decreased FoxO protein levels. Consistently, the FoxO targets, Sod2 and catalase, were significantly down-regulated in $\It{Mst1^{-/-}}$ T cells, thereby resulting in elevated levels of intracellular reactive oxygen species (ROS) and induction of apoptosis. Expression of constitutively active FoxO3a restored $\It{Mst1^{-/-}}$ T cell survival. Crossing Mst1 transgenic mice (Mst1 Tg) with $\It{Mst1^{-/-}}$ mice reduced ROS levels and restored normal numbers of peripheral naive T cells in Mst1 Tg; $\It{Mst1^{-/-}}$ progeny. Interestingly, peripheral T cells from $\It{Mst1^{-/-}}$ mice were hypersensitive to $\gamma$-irradiation and paraquat-induced oxidative stresses, whereas those from Mst1 Tg mice were resistant. These data support the hypothesis that tolerance to increased levels of intracellular ROS provided by the Mst1-FoxOs signaling pathway is crucial for the maintenance of $na\ddot{i}ve$ T cell homeostasis in the periphery. However, $\It{Mst2^{-/-}}$ T cells did not show any defects seen in $\It{Mst1^{-/-}}$ T cells. This implies that MST1 has more major functions than MST2 does in maintaining naive T cell homeostasis. And although MST1 and MST2 also function in apoptotic stress, MEFs from $\It{Mst1^{-/-}}$ and $\It{Mst2^{-/-}}$mice showed normal apoptotic responses t... | eng |
dc.language | eng | - |
dc.publisher | 한국과학기술원 | - |
dc.subject | MST2 | - |
dc.subject | MST1 | - |
dc.subject | Mice | - |
dc.subject | 생쥐 | - |
dc.subject | MST2 | - |
dc.subject | MST1 | - |
dc.title | Functional studies on MST1 and MST2 kinases in mice | - |
dc.title.alternative | 생쥐 모델을 이용한 MST1/2 Kinase 단백질의 역할 규명 | - |
dc.type | Thesis(Ph.D) | - |
dc.identifier.CNRN | 418771/325007 | - |
dc.description.department | 한국과학기술원 : 생명과학과, | - |
dc.identifier.uid | 020045158 | - |
dc.contributor.localauthor | Lim, Dae-Sik | - |
dc.contributor.localauthor | 임대식 | - |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.