title: C-FLIPLModulated Wnt/β-Catenin Activation via Association with TIP49 Protein.
abstract: Cellular FLICE-like inhibitory protein (c-FLIPL) is a key inhibitory protein in the extrinsic apoptotic pathway. Recent studies showed that c-FLIPLcould translocate into the nucleus and might be involved in the Wnt signaling pathway. The nuclear function of c-FLIPLwas still unclear. Here we found a novel c-FLIPL-associated protein TIP49, which is a nuclear protein identified as a cofactor in the transcriptional regulation of β-catenin. They had co-localization in the nucleus and the DED domain of c-FLIPLwas required for the association with TIP49. By performing ChIP experiments, C-FLIPLwas detected in the ITF-2 locus and facilitated TIP49 accumulation in the formation of complexes at the T-cell-specific transcription factor site of human ITF-2 promoter. When TIP49 knockdown, c-FLIPL-driven Wnt activation, and cell proliferation were inhibited, suggesting that a role of nuclear c-FLIPLinvolved in modulation of the Wnt pathway was in a TIP49-dependent manner. Elevated expression of c-FLIPLand TIP49 that coincided in human lung cancers were analyzedin silicousing the Oncomine database. Their high expressions were reconfirmed in six lung cancer cell lines and correlated with cell growth. The association of c-FLIPLand TIP49 provided an additional mechanism involved in c-FLIPL-mediated functions, including Wnt activation.
authors.affiliation: From The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, Jiangsu and jzhang08@nju.edu.cn.|the Changzhou High-Tech Research Institute of Nanjing University and Jiangsu Target Pharma Laboratories Inc., Changzhou 213164, Jiangsu, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: From The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, Jiangsu and.
authors.forename: Heng-Yi
authors.initials: HY
authors.lastname: Jiang
authors.affiliation: From The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, Jiangsu and.
authors.forename: Lin-Kai
authors.initials: LK
authors.lastname: Zhang
authors.affiliation: From The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, Jiangsu and.
authors.forename: Wen-Ling
authors.initials: WL
authors.lastname: Xu
authors.affiliation: From The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, Jiangsu and.
authors.forename: Yi-Ting
authors.initials: YT
authors.lastname: Qiao
authors.affiliation: From The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, Jiangsu and.
authors.forename: Xu-Guo
authors.initials: XG
authors.lastname: Zhu
authors.affiliation: From The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, Jiangsu and.
authors.forename: Wan
authors.initials: W
authors.lastname: Liu
authors.affiliation: From The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, Jiangsu and.
authors.forename: Qian-Qian
authors.initials: QQ
authors.lastname: Zheng
authors.affiliation: From The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, Jiangsu and zchua@nju.edu.cn.|the Changzhou High-Tech Research Institute of Nanjing University and Jiangsu Target Pharma Laboratories Inc., Changzhou 213164, Jiangsu, People's Republic of China.
authors.forename: Zi-Chun
authors.initials: ZC
authors.lastname: Hua
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D000818:Animals; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D011485:Protein Binding; D020798:Two-Hybrid System Techniques; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D002352:Carrier Proteins; D051153:Wnt Proteins; D051176:beta Catenin; D000074183:ATPases Associated with Diverse Cellular Activities; D004265:DNA Helicases; C486549:RUVBL1 protein, human
keywords: TIP49; beta-catenin (β-catenin); c-FLIP; cancer biology; cell growth; nuclear translocation; transcription coactivator