A GAPDH serotonylation system couples CD8 + T cell glycolytic metabolism to antitumor immunity.

Autor:	Wang X; Department of Radiation Oncology, Cancer Institute of Jiangsu University, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, P.R. China. Electronic address: jsdxwx@126.com., Fu SQ; Department of Radiation Oncology, Cancer Institute of Jiangsu University, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, P.R. China., Yuan X; Department of Radiation Oncology, Cancer Institute of Jiangsu University, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, P.R. China., Yu F; School of Life Sciences, Jiangsu University, Zhenjiang 212013, P.R. China., Ji Q; Department of Radiation Oncology, Cancer Institute of Jiangsu University, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, P.R. China., Tang HW; Department of Radiation Oncology, Cancer Institute of Jiangsu University, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, P.R. China., Li RK; Department of Radiation Oncology, Cancer Institute of Jiangsu University, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, P.R. China., Huang S; State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, P.R. China., Huang PQ; State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, P.R. China., Qin WT; State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, P.R. China., Zuo H; School of Life Sciences, Jiangsu University, Zhenjiang 212013, P.R. China., Du C; State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, P.R. China., Yao LL; State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, P.R. China., Li H; State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, P.R. China., Li J; State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, P.R. China., Li DX; State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, P.R. China., Yang Y; State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, P.R. China., Xiao SY; State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, P.R. China., Tulamaiti A; State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, P.R. China., Wang XF; Department of Radiation Oncology, Cancer Institute of Jiangsu University, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, P.R. China., Dai CH; Department of Radiation Oncology, Cancer Institute of Jiangsu University, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, P.R. China., Zhang X; Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang 212013, P.R. China. Electronic address: xuzhang@ujs.edu.cn., Jiang SH; State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, P.R. China. Electronic address: shjiang@shsci.org., Hu LP; State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, P.R. China. Electronic address: lphu@shsci.org., Zhang XL; State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, P.R. China. Electronic address: xlzhang@shsci.org., Zhang ZG; State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, P.R. China. Electronic address: zzhang@shsci.org.
Jazyk:	angličtina
Zdroj:	Molecular cell [Mol Cell] 2024 Feb 15; Vol. 84 (4), pp. 760-775.e7. Date of Electronic Publication: 2024 Jan 11.
DOI:	10.1016/j.molcel.2023.12.015
Abstrakt:	Apart from the canonical serotonin (5-hydroxytryptamine [5-HT])-receptor signaling transduction pattern, 5-HT-involved post-translational serotonylation has recently been noted. Here, we report a glyceraldehyde-3-phosphate dehydrogenase (GAPDH) serotonylation system that promotes the glycolytic metabolism and antitumor immune activity of CD8 + T cells. Tissue transglutaminase 2 (TGM2) transfers 5-HT to GAPDH glutamine 262 and catalyzes the serotonylation reaction. Serotonylation supports the cytoplasmic localization of GAPDH, which induces a glycolytic metabolic shift in CD8 + T cells and contributes to antitumor immunity. CD8 + T cells accumulate intracellular 5-HT for serotonylation through both synthesis by tryptophan hydroxylase 1 (TPH1) and uptake from the extracellular compartment via serotonin transporter (SERT). Monoamine oxidase A (MAOA) degrades 5-HT and acts as an intrinsic negative regulator of CD8 + T cells. The adoptive transfer of 5-HT-producing TPH1-overexpressing chimeric antigen receptor T (CAR-T) cells induced a robust antitumor response. Our findings expand the known range of neuroimmune interaction patterns by providing evidence of receptor-independent serotonylation post-translational modification. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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