title: Interaction with Ppil3 leads to the cytoplasmic localization of Apoptin in tumor cells.
abstract: Apoptin, a small protein encoded by chicken anemia virus (CAV), induces cell death specifically in cancer cells. In normal cells, Apoptin remains in the cytoplasm; whereas in cancerous cells, it migrates into the nucleus and kills the cell. Cellular localization appears to be crucial. Through a yeast two-hybrid screen, we identified human Peptidyl-prolyl isomerase-like 3 (Ppil3) as one of the Apoptin-associated proteins. Ppil3 could bind Apoptin directly, and held Apoptin in cytoplasm even in tumor cells. We then demonstrated that the nuclearcytoplasmic distribution of Apoptin is related to the expression level of intrinsic Ppil3. Moreover, extrinsic modifying of Ppil3 levels also resulted in nuclearcytoplasmic shuffling of Apoptin. The Apoptin P109A mutant, located between the putative nuclear localization and export signals, could significantly impair the function of Ppil3. Our results suggest a new direction for the localization mechanism study of Apoptin in cells.
authors.affiliation: The Key Laboratory of Gene Engineering of Ministry of Education, School of Life Sciences, Sun Yat-Sen (Zhongshan) University, 135th Xin-Gang-Xi Road, Guangzhou 510275, PR China.
authors.forename: De-Hua
authors.initials: DH
authors.lastname: Huo
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Yi
authors.forename: Jine
authors.initials: J
authors.lastname: Yang
mesh_terms: D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D036022:Capsid Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D021983:Cyclophilins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D003593:Cytoplasm / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009369:Neoplasms / Q000201:enzymology / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
chemical_list: D036022:Capsid Proteins; C091717:VP3 protein, Chicken anemia virus; D021983:Cyclophilins; C503209:PPIL3 protein, human