SUMO2/3 modification of activating transcription factor 5 (ATF5) controls its dynamic translocation at the centrosome
| Autor: | Ming Hu, Kathy Lengel, Eugene Y. Kim, Henning Knipprath, Edward Liu, Yunsheng Yuan, Kari A. Gaither, Bin Wang, David Liu, Yidi Xu, Dongmeng Qian |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cell cycle checkpoint Recombinant Fusion Proteins Green Fluorescent Proteins Activating transcription factor SUMO protein Centrosome cycle Biology Biochemistry Genomic Instability Cell Line 03 medical and health sciences PCNT Consensus Sequence Animals Humans Amino Acid Sequence Ubiquitins Molecular Biology Transcription factor Conserved Sequence Centrosome Sumoylation Cell Biology Cell cycle Activating Transcription Factors Peptide Fragments Cell biology Protein Transport 030104 developmental biology Amino Acid Substitution Microscopy Fluorescence Mutation Mutagenesis Site-Directed Small Ubiquitin-Related Modifier Proteins RNA Interference Gene Deletion |
| Zdroj: | Journal of Biological Chemistry. 293:2939-2948 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.ra117.001151 |
| Popis: | Activating transcription factor 5 (ATF5) is a member of the ATF/cAMP response element–binding protein family of transcription factors. ATF5 regulates stress responses and cell survival, proliferation, and differentiation and also plays a role in viral infections, cancer, diabetes, schizophrenia, and the olfactory system. Moreover, it was found to also have a critical cell cycle–dependent structural function at the centrosome. However, the mechanism that controls the localization of ATF5 at the centrosome is unclear. Here we report that ATF5 is small ubiquitin-like modifier (SUMO) 2/3–modified at a conserved SUMO-targeting consensus site in various types of mammalian cells. We found that SUMOylation of ATF5 is elevated in the G(1) phase of the cell cycle and diminished in the G(2)/M phase. ATF5 SUMOylation disrupted the interaction of ATF5 with several centrosomal proteins and dislodged ATF5 from the centrosome at the end of the M phase. Of note, blockade of ATF5 SUMOylation deregulated the centrosome cycle, impeded ATF5 translocation from the centrosome, and caused genomic instability and G(2)/M arrest in HeLa cells. Our results indicate that ATF5 SUMOylation is an essential mechanism that regulates ATF5 localization and function at the centrosome. |
| Databáze: | OpenAIRE |
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