title: Altered dynamics of ubiquitin hybrid proteins during tumor cell apoptosis.
abstract: The ubiquitin hybrid genes Uba80 and Uba52 encode ubiquitin (Ub), which is fused to the ribosomal proteins S27a (RPS27a) and L40 (RPL40), respectively. Here, we show that these genes are preferentially over-expressed during hepatoma cell apoptosis. Experiments using the tet-inducible transgenic system revealed that over-expression of the ubiquitin hybrid genes sensitized the cells to apoptosis. Further analysis suggested that Ub, and not RPS27a or RPL40, was associated with apoptotic cell death. Cleavage-resistant mutation analysis revealed that the N-terminal portion and the last two amino acids (GG) of Ub are critical for cleavage at the junction between the two protein moieties. An apoptogenic stimulus enhances the nuclear targeting and aggregation of Ub in the nucleus, resulting in histone H2A deubiquitylation followed by abnormal ubiquitylation of the nuclear envelope and the lamina. These events accompany the apoptotic nuclear morphology in the late stage of apoptosis. Each fused RP is localized in the nucleoli. These results suggest a role for Ub hybrid proteins in the altered nuclear dynamics of Ub during tumor cell apoptosis induced by apoptogenic stimuli.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Institute for Medical Science, Chonbuk National University Medical School and Hospital, Jeonju, South Korea.
authors.forename: X-J
authors.initials: XJ
authors.lastname: Han
authors.forename: M-J
authors.initials: MJ
authors.lastname: Lee
authors.forename: G-R
authors.initials: GR
authors.lastname: Yu
authors.forename: Z-W
authors.initials: ZW
authors.lastname: Lee
authors.forename: J-Y
authors.initials: JY
authors.lastname: Bae
authors.forename: Y-C
authors.initials: YC
authors.lastname: Bae
authors.forename: S-H
authors.initials: SH
authors.lastname: Kang
authors.forename: D-G
authors.initials: DG
authors.lastname: Kim
mesh_terms: D020816:Amino Acid Motifs; D017209:Apoptosis; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D020287:In Situ Nick-End Labeling; D016086:Lentivirus; D008156:Luciferases; D050506:Mutant Chimeric Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D034741:RNA, Small Interfering; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014161:Transduction, Genetic; D054875:Ubiquitination; D014452:Ubiquitins / Q000235:genetics / Q000378:metabolism*
chemical_list: D006657:Histones; D050506:Mutant Chimeric Proteins; D034741:RNA, Small Interfering; D012269:Ribosomal Proteins; D014452:Ubiquitins; C096227:ribosomal protein S27a; D008156:Luciferases