دورية أكاديمية
The alanyl-tRNA synthetase AARS1 moonlights as a lactyltransferase to promote YAP signaling in gastric cancer.
| العنوان: | The alanyl-tRNA synthetase AARS1 moonlights as a lactyltransferase to promote YAP signaling in gastric cancer. |
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| المؤلفون: | Ju J; Department of Medical Ultrasound and Department of Stomatology, Shanghai Tenth People's Hospital, Tongji University Cancer Center, Tongji University School of Medicine, Shanghai, China., Zhang H; State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai, China., Lin M; Department of General Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai, China., Yan Z; State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai, China.; School of Life Science, Inner Mongolia University, Hohhot, Inner Mongolia, China., An L; Department of Medical Ultrasound and Department of Stomatology, Shanghai Tenth People's Hospital, Tongji University Cancer Center, Tongji University School of Medicine, Shanghai, China., Cao Z; Department of Medical Ultrasound and Department of Stomatology, Shanghai Tenth People's Hospital, Tongji University Cancer Center, Tongji University School of Medicine, Shanghai, China., Geng D; School of Medicine, Anhui University of Science and Technology, Huainan, China., Yue J; State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai, China., Tang Y; Department of Medical Ultrasound and Department of Stomatology, Shanghai Tenth People's Hospital, Tongji University Cancer Center, Tongji University School of Medicine, Shanghai, China., Tian L; State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai, China., Chen F; State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai, China., Han Y; Department of Medical Ultrasound and Department of Stomatology, Shanghai Tenth People's Hospital, Tongji University Cancer Center, Tongji University School of Medicine, Shanghai, China., Wang W; State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai, China., Zhao S; State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai, China., Jiao S; State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai, China., Zhou Z; State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai, China.; Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, China. |
| المصدر: | The Journal of clinical investigation [J Clin Invest] 2024 Mar 21; Vol. 134 (10). Date of Electronic Publication: 2024 Mar 21. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Society for Clinical Investigation Country of Publication: United States NLM ID: 7802877 Publication Model: Electronic Cited Medium: Internet ISSN: 1558-8238 (Electronic) Linking ISSN: 00219738 NLM ISO Abbreviation: J Clin Invest Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 1999- : Ann Arbor, MI : American Society for Clinical Investigation Original Publication: New Haven [etc.] American Society for Clinical Investigation. |
| مواضيع طبية MeSH: | Signal Transduction* , Stomach Neoplasms*/enzymology , Stomach Neoplasms*/genetics , Stomach Neoplasms*/pathology , Transcription Factors*/metabolism , Transcription Factors*/genetics , YAP-Signaling Proteins*/metabolism , YAP-Signaling Proteins*/genetics , Alanine-tRNA Ligase*/genetics , Alanine-tRNA Ligase*/metabolism, Animals ; Humans ; Mice ; Adaptor Proteins, Signal Transducing/metabolism ; Adaptor Proteins, Signal Transducing/genetics ; Amino Acyl-tRNA Synthetases/metabolism ; Amino Acyl-tRNA Synthetases/genetics ; Cell Line, Tumor ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Lactic Acid/metabolism ; Neoplasm Proteins/metabolism ; Neoplasm Proteins/genetics |
| مستخلص: | Lactylation has been recently identified as a new type of posttranslational modification occurring widely on lysine residues of both histone and nonhistone proteins. The acetyltransferase 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 of whether p300 is a genuine lactyltransferase. Here, we report that alanyl-tRNA synthetase 1 (AARS1) moonlights as a bona fide lactyltransferase that directly uses lactate and ATP to catalyze protein lactylation. Among the candidate substrates, we focused on the Hippo pathway, which has a well-established role in tumorigenesis. Specifically, AARS1 was found to sense intracellular lactate and translocate into the nucleus to lactylate and activate the 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 patients with GC. Collectively, this work found AARS1 with lactyltransferase activity in vitro and in vivo and revealed how the metabolite lactate is translated into a signal of cell proliferation. |
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| فهرسة مساهمة: | Keywords: Cancer; Metabolism |
| المشرفين على المادة: | 0 (Adaptor Proteins, Signal Transducing) EC 6.1.1.- (Amino Acyl-tRNA Synthetases) 33X04XA5AT (Lactic Acid) 0 (Neoplasm Proteins) 0 (Transcription Factors) 0 (YAP-Signaling Proteins) EC 6.1.1.7 (AARS1 protein, human) EC 6.1.1.7 (Alanine-tRNA Ligase) |
| تواريخ الأحداث: | Date Created: 20240321 Date Completed: 20240515 Latest Revision: 20240603 |
| رمز التحديث: | 20240604 |
| مُعرف محوري في PubMed: | PMC11093599 |
| DOI: | 10.1172/JCI174587 |
| PMID: | 38512451 |
| قاعدة البيانات: | MEDLINE |
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