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Patt1, a novel protein acetyltransferase that is highly expressed in liver and downregulated in hepatocellular carcinoma,enhances apoptosis of hepatoma cells
Authors:Zhen Liu  Yang Liu  Huiqiang Wang  Xinjian Ge  Qihuang Jin  Guanghui Ding  Yanan Hu  Ben Zhou  Zhongjian Chen  Xuemei Ge  Baohua Zhang  Xiaobo Man  Qiwei Zhai
Institution:1. Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, and Graduate School of the Chinese Academy of Sciences, 294 Taiyuan Road, Shanghai 200031, China;2. Department of Hepatobiliary Surgery, Shanghai Tenth People''s Hospital, Tongji University School of Medicine, Shanghai 200072, China;3. Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China;1. Department of Molecular Biology, University of Bergen, N-5020 Bergen, Norway;2. Department of Surgery, Haukeland University Hospital, N-5021 Bergen, Norway;1. Department of Chemistry, Duke University, Durham, NC, USA;2. Trinity College of Arts & Sciences, Duke University, Durham, NC, USA;3. Duke University Human Vaccine Institute Macromolecular Crystallography Center, Duke University School of Medicine, Durham, NC, USA;1. Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA;2. Department of Life Sciences, Phohang University of Science and Technology, Phohang, Gyeong-buk 790-784, South Korea;1. CNRS, Institut des Sciences du Végétal, 1 Avenue de la Terrasse, Bât 23A, F-91198 Gif sur Yvette, France;2. Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Sud, 1 Avenue de la Terrasse, 91198 Gif-sur-Yvette cedex, France;1. Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan;2. Department of Medical Education and Research, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan;3. TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei, Taiwan;4. Department of Urology, School of Medicine, Taipei Medical University, Taipei, Taiwan;5. The Genomics Research Center, Academia Sinica, Taipei, Taiwan;6. Graduate Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan;7. Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan;8. Department of Agricultural Chemistry, National Taiwan University, Taipei, Taiwan;9. Department of Urology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan;10. Department of Biochemistry, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan;3. Department of Molecular Biology, University of Bergen, N-5020 Bergen;4. Computational Biology Unit, Department of Informatics, University of Bergen, N-5020 Bergen;5. Department of Surgery, Haukeland University Hospital, N-5021 Bergen, Norway
Abstract:Protein acetylation is increasingly recognized as an important post-translational modification. Although a lot of protein acetyltransferases have been identified, a few putative acetyltransferases are yet to be studied. In this study, we identified a novel protein acetyltransferase, Patt1, which belongs to GNAT family. Patt1 exhibited histone acetyltransferase activity and auto-acetylation activity. Deletion and mutation analysis of the predicted acetyltransferase domain in Patt1 showed that the conserved Glu139 was an important residue for its protein acetyltransferase activity. Furthermore, we found that Patt1 was highly expressed in liver and significantly downregulated in hepatocellular carcinoma tissues. In addition, we showed that overexpression of Patt1 enhanced the apoptosis of hepatoma cells dependent on its acetyltransferase activity, whereas knockdown of Patt1 significantly protected Chang liver cells from apoptosis. These data suggest that Patt1 might be involved in the development of hepatocellular carcinoma, and could be served as a potential therapy target for hepatocellular carcinoma.
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