DNA Damage–Dependent Translocation of B23 and p19ARF Is Regulated by the Jun N-Terminal Kinase Pathway
| Autor: | Orli Yogev, Eitan Shaulian, Kazushi Inoue, Keren Saadon, Shira Anzi |
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| Rok vydání: | 2008 |
| Předmět: |
Threonine
Cancer Research MAP Kinase Kinase 4 Ultraviolet Rays Nucleolus DNA repair DNA damage Chromosomal translocation Biology Models Biological Humans Phosphorylation Cellular Senescence Cyclin-Dependent Kinase Inhibitor p16 Activator (genetics) Kinase JNK Mitogen-Activated Protein Kinases Nuclear Proteins Molecular biology Transport protein Gene Expression Regulation Neoplastic Protein Transport Oncology Nucleophosmin Cell Nucleolus DNA Damage |
| Zdroj: | Cancer Research. 68:1398-1406 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/0008-5472.can-07-2865 |
| Popis: | The dynamic behavior of the nucleolus plays a role in the detection of and response to DNA damage of cells. Two nucleolar proteins, p14ARF/p19ARF and B23, were shown to translocate out of the nucleolus after exposure of cells to DNA-damaging agents. This translocation affects multiple cellular functions, such as DNA repair, proliferation, and survival. In this study, we identify a pathway and scrutinize the mechanisms leading to the translocation of these proteins after exposure of cells to DNA-damaging agents. We show that redistribution of B23 and p19ARF after the exposure to genotoxic stress occurs preferentially when the c-Jun-NH2-kinase (JNK) pathway is activated and is inhibited when the JNK pathway is impaired. The stress-induced translocation of alternative reading frame (ARF) is JNK dependent and mediated by two activator proteins, c-Jun and JunB. Thr91 and Thr93 of c-Jun are required for the translocation, but the transcriptional activity of c-Jun is dispensable. Instead, c-Jun interacts with B23 in a dose-dependent manner. c-Jun itself is excluded from the nucleolus in a JNK-dependent manner. Hence, we suggest that c-Jun translocates B23 and ARF from the nucleolus after JNK activation by means of protein interactions. In senescent cells, JNK activity and c-Jun levels are reduced concomitantly with ARF nucleolar accumulation, and UV radiation does not cause the translocation of ARF. [Cancer Res 2008;68(5):1398–406] |
| Databáze: | OpenAIRE |
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