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ResearchIn-Press PreviewMetabolism Open Access | 10.1172/JCI174587
1Department of Medical Ultrasound, Department of Stomatology, Shanghai Tenth People's Hospital, Tongji University Cancer Center, Tongji University School of Medicine, Shanghai, China
2State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai, China
3Department of General Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai, China
4School of Medicine, Anhui University of Science and Technology, Huainan, China
Find articles by Ju, J. in: JCI | PubMed | Google Scholar
1Department of Medical Ultrasound, Department of Stomatology, Shanghai Tenth People's Hospital, Tongji University Cancer Center, Tongji University School of Medicine, Shanghai, China
2State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai, China
3Department of General Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai, China
4School of Medicine, Anhui University of Science and Technology, Huainan, China
Find articles by Zhang, H. in: JCI | PubMed | Google Scholar
1Department of Medical Ultrasound, Department of Stomatology, Shanghai Tenth People's Hospital, Tongji University Cancer Center, Tongji University School of Medicine, Shanghai, China
2State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai, China
3Department of General Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai, China
4School of Medicine, Anhui University of Science and Technology, Huainan, China
Find articles by Lin, M. in: JCI | PubMed | Google Scholar
1Department of Medical Ultrasound, Department of Stomatology, Shanghai Tenth People's Hospital, Tongji University Cancer Center, Tongji University School of Medicine, Shanghai, China
2State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai, China
3Department of General Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai, China
4School of Medicine, Anhui University of Science and Technology, Huainan, China
Find articles by Yan, Z. in: JCI | PubMed | Google Scholar
1Department of Medical Ultrasound, Department of Stomatology, Shanghai Tenth People's Hospital, Tongji University Cancer Center, Tongji University School of Medicine, Shanghai, China
2State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai, China
3Department of General Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai, China
4School of Medicine, Anhui University of Science and Technology, Huainan, China
Find articles by An, L. in: JCI | PubMed | Google Scholar
1Department of Medical Ultrasound, Department of Stomatology, Shanghai Tenth People's Hospital, Tongji University Cancer Center, Tongji University School of Medicine, Shanghai, China
2State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai, China
3Department of General Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai, China
4School of Medicine, Anhui University of Science and Technology, Huainan, China
Find articles by Cao, Z. in: JCI | PubMed | Google Scholar |
1Department of Medical Ultrasound, Department of Stomatology, Shanghai Tenth People's Hospital, Tongji University Cancer Center, Tongji University School of Medicine, Shanghai, China
2State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai, China
3Department of General Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai, China
4School of Medicine, Anhui University of Science and Technology, Huainan, China
Find articles by Geng, D. in: JCI | PubMed | Google Scholar
1Department of Medical Ultrasound, Department of Stomatology, Shanghai Tenth People's Hospital, Tongji University Cancer Center, Tongji University School of Medicine, Shanghai, China
2State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai, China
3Department of General Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai, China
4School of Medicine, Anhui University of Science and Technology, Huainan, China
Find articles by Yue, J. in: JCI | PubMed | Google Scholar
1Department of Medical Ultrasound, Department of Stomatology, Shanghai Tenth People's Hospital, Tongji University Cancer Center, Tongji University School of Medicine, Shanghai, China
2State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai, China
3Department of General Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai, China
4School of Medicine, Anhui University of Science and Technology, Huainan, China
Find articles by Tang, Y. in: JCI | PubMed | Google Scholar
1Department of Medical Ultrasound, Department of Stomatology, Shanghai Tenth People's Hospital, Tongji University Cancer Center, Tongji University School of Medicine, Shanghai, China
2State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai, China
3Department of General Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai, China
4School of Medicine, Anhui University of Science and Technology, Huainan, China
Find articles by Tian, L. in: JCI | PubMed | Google Scholar
1Department of Medical Ultrasound, Department of Stomatology, Shanghai Tenth People's Hospital, Tongji University Cancer Center, Tongji University School of Medicine, Shanghai, China
2State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai, China
3Department of General Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai, China
4School of Medicine, Anhui University of Science and Technology, Huainan, China
Find articles by Chen, F. in: JCI | PubMed | Google Scholar
1Department of Medical Ultrasound, Department of Stomatology, Shanghai Tenth People's Hospital, Tongji University Cancer Center, Tongji University School of Medicine, Shanghai, China
2State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai, China
3Department of General Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai, China
4School of Medicine, Anhui University of Science and Technology, Huainan, China
Find articles by Han, Y. in: JCI | PubMed | Google Scholar
1Department of Medical Ultrasound, Department of Stomatology, Shanghai Tenth People's Hospital, Tongji University Cancer Center, Tongji University School of Medicine, Shanghai, China
2State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai, China
3Department of General Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai, China
4School of Medicine, Anhui University of Science and Technology, Huainan, China
Find articles by Wang, W. in: JCI | PubMed | Google Scholar
1Department of Medical Ultrasound, Department of Stomatology, Shanghai Tenth People's Hospital, Tongji University Cancer Center, Tongji University School of Medicine, Shanghai, China
2State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai, China
3Department of General Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai, China
4School of Medicine, Anhui University of Science and Technology, Huainan, China
Find articles by Zhao, S. in: JCI | PubMed | Google Scholar
1Department of Medical Ultrasound, Department of Stomatology, Shanghai Tenth People's Hospital, Tongji University Cancer Center, Tongji University School of Medicine, Shanghai, China
2State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai, China
3Department of General Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai, China
4School of Medicine, Anhui University of Science and Technology, Huainan, China
Find articles by Shi, J. in: JCI | PubMed | Google Scholar
1Department of Medical Ultrasound, Department of Stomatology, Shanghai Tenth People's Hospital, Tongji University Cancer Center, Tongji University School of Medicine, Shanghai, China
2State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai, China
3Department of General Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai, China
4School of Medicine, Anhui University of Science and Technology, Huainan, China
Find articles by Zhou, Z. in: JCI | PubMed | Google Scholar
Published March 21, 2024 - More info
Lactylation has been recently identified as a new type of posttranslational modification widely occurring on lysine residues of both histone and non-histone proteins. The acetyl transferase p300 is thought to mediate protein lactylation, yet the cellular concentration of the proposed lactyl-donor, lactyl-coenzyme A is about 1,000 times lower than that of acetyl-CoA, raising the question whether p300 is a genuine lactyl-transferase. Here, we report the Alanyl-tRNA synthetase 1 (AARS1) moonlights as a bona fide lactyl-transferase that directly uses lactate and ATP to catalyze protein lactylation. Among the candidate substrates, we focused on the Hippo pathway that has a well-established role in tumorigenesis. Specifically, AARS1 was found to sense intracellular lactate and translocate into the nucleus to lactylate and activate YAP-TEAD complex; and AARS1 itself was identified as a Hippo target gene that forms a positive feedback loop with YAP-TEAD to promote gastric cancer (GC) cell proliferation. Consistently, the expression of AARS1 was found to be upregulated in GC, and elevated AARS1 expression was found to be associated with poor prognosis for GC patients. Collectively, this work discovered AARS1 with lactyl-transferase activity in vitro and in vivo and revealed how the metabolite lactate is translated into a signal of cell proliferation.