Characterization of tumor suppressor LKB1 signaling pathway in vivo = 항암 유전자 LKB1 신호 전달계의 생체 내 기능 연구

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LKB1 is a serine/threonine kinase that functions as a master tumor suppressor in the small intestine. Although numerous molecular and biochemical studies have implicated LKB1 in a variety function of cellular processes, little is known about the tumor suppressing mechanism of LKB1 in vivo. Therefore, I performed genetic modifier screening in Drosophila to discover the novel proteins involved in tumor suppressor LKB1 signaling pathway in vivo. Subsequently, I identified Silnoon (Sln) as a novel LKB1-interacting gene, which is a monocarboxylate transporter (MCT) mediating the influx of extra-cellular butyrate. Surprisingly, Sln induces ectopic apoptosis, which is enhanced by co-expression of LKB1 as well as butyrate treatment. In contrast, downregulation of Sln suppressed LKB1-dependent apoptosis and caused a drastic brain hyperplasia phenotype as observed in the LKB1-null mutant. Moreover, ectopic expression of Sln was sufficient to suppress the brain hyperplasia phenotype of LKB1-null mutant, demonstrating that Sln is a downstream effector of the LKB1 signaling pathway. Finally, I showed that LKB1 kinase activity affects the subcellular localization of Sln during eye morphogenesis. Since some monocarboxylate transporters are involved in the cancer development as a tumor, I suggest a plausible synapse between the two tumor suppressing mechanisms, LKB1 and MCT, which however were known be unlinked.
Advisors
Chung, Jong-kyeongresearcher정종경researcher
Description
한국과학기술원 : 생명과학과,
Publisher
한국과학기술원
Issue Date
2006
Identifier
301302/325007  / 020043516
Language
eng
Description

학위논문(석사) - 한국과학기술원 : 생명과학과, 2006.2, [ vii, 57 p. ]

Keywords

tumor suppressor LKB1; 항암 유전자 엘케이비1

URI
http://hdl.handle.net/10203/28101
Link
http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=301302&flag=dissertation
Appears in Collection
BS-Theses_Master(석사논문)
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