title: L1-ORF1p, a Smad4 interaction protein, promotes proliferation of HepG2 cells and tumorigenesis in mice.
abstract: Long interspersed nucleotide element (LINE-1; L1) as an autonomous retrotransposon is localized usually in AT-rich, low-recombined, and gene-poor regions of genome. It is transiently activated in embryonic development and continuously activated in all tumor cells tested so far. Full-length L1 gene contains 5' untranslated region, two open reading frames (ORFs) encoded L1ORF1p and L1ORF2p, and a 3' terminal polyadenylation site. Compared with L1ORF2p, a protein encompassing reverse transcriptase and endonuclease activities, L1ORF1p remains to be elucidated. With liver cancer cells and tissues, the expression and sub-localization of L1ORF1p were investigated and shown that L1-ORF1p expresses just in liver cancer cells and tissues but not in normal liver cells and almost not in adjacent tissues. To characterize L1ORF1p, the strategies for over-expression and down-regulation of L1ORF1p in transfected cells were implemented. The phenomenon of promoting cell proliferation and colony formation was observed in transfected cells with L1ORF1p over-expression and vice versa. Down-regulation of L1ORF1p suppresses tumorigenesis in vitro and in vivo. Smad4 as an interaction protein of L1ORF1p is identified for the first time, while L1ORF1p is responsible for Smad4 sequestration in the cytoplasm. Thus, L1ORF1p contributed to tumorigenesis and may attribute to, at least partly, its participation in Smad4-signaling regulation.
authors.affiliation: The Institute of Life Sciences and Bio-Engineering in Beijing Jiaotong University, Beijing, China. zhuyf2004@163.com
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Zhu
authors.forename: Fan
authors.initials: F
authors.lastname: Feng
authors.forename: Jiyun
authors.initials: J
authors.lastname: Yu
authors.forename: Bin
authors.initials: B
authors.lastname: Song
authors.forename: Mingming
authors.initials: M
authors.lastname: Hu
authors.forename: Xudong
authors.initials: X
authors.lastname: Gao
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D020121:5' Untranslated Regions; D000818:Animals; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D003593:Cytoplasm / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human; D057809:HEK293 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics; D008114:Liver Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016366:Open Reading Frames; D025941:Protein Interaction Mapping; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism*; D051901:Smad4 Protein / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D020121:5' Untranslated Regions; C494023:L1 ORF1 protein, human; D012261:Ribonucleoproteins; C497796:SMAD4 protein, human; D051901:Smad4 Protein; D016212:Transforming Growth Factor beta