1. Altered dynamics of ubiquitin hybrid proteins during tumor cell apoptosis
- Author
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Seong Ho Kang, Lee Mj, Xue-Ji Han, Yu Gr, Lee Zw, Ji-Eun Bae, Kim Dg, and Yong Chul Bae
- Subjects
Ribosomal Proteins ,Cancer Research ,Nucleolus ,Immunology ,tumor cells ,Amino Acid Motifs ,Mutant Chimeric Proteins ,Apoptosis ,ubiquitin hybrid proteins ,apoptosis ,H2A histone ,ubiquitylation ,deubiquitylation ,Histones ,Cellular and Molecular Neuroscience ,Ubiquitin ,Ribosomal protein ,Genes, Reporter ,Transduction, Genetic ,Cell Line, Tumor ,Neoplasms ,Histone H2A ,medicine ,In Situ Nick-End Labeling ,Humans ,RNA, Small Interfering ,Luciferases ,Ubiquitins ,Cell Nucleus ,biology ,Lentivirus ,Ubiquitination ,Cell Biology ,Molecular biology ,Cell biology ,Gene Expression Regulation, Neoplastic ,Cell nucleus ,Histone ,medicine.anatomical_structure ,Mutation ,biology.protein ,Original Article ,Signal transduction ,Signal Transduction - 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. Cell Death and Disease (2012) 3, e255; doi:10.1038/cddis.2011.142; published online 19 January 2012
- Published
- 2012