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LZTS2 Regulation by PKCK2 modulates Wnt signaling
DC Field | Value | Language |
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dc.contributor.author | 이윤미 | - |
dc.date.accessioned | 2015-11-21T07:47:19Z | - |
dc.date.available | 2015-11-21T07:47:19Z | - |
dc.date.issued | 2010 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/125128 | - |
dc.description | 의과학과/박사 | - |
dc.description.abstract | Protein kinase casein kinase 2 (PKCK2) is a constitutively active serine/threonine kinase overexpressed in many types of human cancer. PKCK2 is a positive regulator in Wnt signaling pathway, since it stabilizes ?-catenin, thereby increasing its nuclear translocation, binding to Tcf/Lef (T-cell factor/lymphoid enhancing factor) components and activating the transcription of Wnt target genes.Leucine zipper putative tumor suppressor 2 (LZTS2) is frequently lost in a variety of human tumors. The LZTS2 interacts with ?-catenin and represses ?-catenin mediated transcription on TCF/LEF, however, little is known about PKCK2 mediated regulation of LZTS2.This study presented the identification of LZTS as a novel binding protein to PKCK2, the role of PKCK2-mediated phosphorylation on LZTS2, and its effect on Wnt signaling. The interaction between LZTS2 and PKCK2 was initially identified by a yeast two-hybrid screening and was further confirmed by GST pull down and co-immunoprecipitation. Mutational analysis and in vitro kinase assay indicate that LZTS2 contains multiple PKCK2 phosphorylation sites. In addition, it is demonstrated that PKCK2 stabilizes LZTS2 by phosphorylation in a proteasome dependent manner. Moreover, PKCK2 inhibition by TBB, a PKCK2 inhibitor, induced an accumulation of LZTS2 in the nucleus which further blocked the translocation of β-catenin from the nucleus to the cytoplasm. Further, PKCK2 activityis required for the regulation of LZTS2-mediated TCF/LEF transcriptional program.Taken together, PKCK2 regulates the LZTS2 stability, and affects the subcellular localization of LZTS2 through its phosphorylation, thereby modulates ?-catenin mediated transcriptional activity in Wnt signaling. | - |
dc.description.statementOfResponsibility | restriction | - |
dc.publisher | 연세대학교 대학원 | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.title | LZTS2 Regulation by PKCK2 modulates Wnt signaling | - |
dc.title.alternative | PKCK2에 의해 조절되는 LZTS2가 Wnt signaling에 미치는 영향 | - |
dc.type | Thesis | - |
dc.identifier.url | https://ymlib.yonsei.ac.kr/catalog/search/book-detail/?cid=CAT000000077652 | - |
dc.contributor.alternativeName | Lee, Yoon Mi | - |
dc.type.local | Dissertation | - |
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