AbstractProper cellular metabolism in T cells is critical for a productive immune response. However, when dysregulated by intrinsic or extrinsic metabolic factors, T cells may contribute to a wide spectrum of diseases, such as cancers and autoimmune diseases. However, the metabolic regulation of T cells remains incompletely understood.

摘要T细胞中适当的细胞代谢对于产生有效的免疫反应至关重要。。然而，T细胞的代谢调节仍然不完全清楚。

Here, we show that MYO1F is required for human and mouse T-cell activation after TCR stimulation and that T-cell-specific Myo1f knockout mice exhibit an increased tumor burden and attenuated EAE severity due to impaired T-cell activation in vivo. Mechanistically, after TCR stimulation, MYO1F is phosphorylated by LCK at tyrosines 607 and 634, which is critical for glyceraldehyde-3-phosphate dehydrogenase (GAPDH) acetylation at Lys84, 86 and 227 mediated by α-TAT1, which is an acetyltransferase, and these processes are important for its activation, cellular glycolysis and thus the effector function of T cells.

在这里，我们显示MYO1F是TCR刺激后人和小鼠T细胞活化所必需的，并且T细胞特异性MYO1F敲除小鼠由于体内T细胞活化受损而表现出增加的肿瘤负荷和减弱的EAE严重性。从机制上讲，TCR刺激后，MYO1F在酪氨酸607和634处被LCK磷酸化，这对于由乙酰转移酶α-TAT1介导的Lys84,86和227处的甘油醛-3-磷酸脱氢酶（GAPDH）乙酰化至关重要，这些过程对于其活化，细胞糖酵解以及因此T细胞的效应功能很重要。

Importantly, we show that a fusion protein of VAV1-MYO1F, a recurrent peripheral T-cell lymphoma (PTCL)-associated oncogenic protein, promotes hyperacetylation of GAPDH and its activation, which leads to aberrant glycolysis and T-cell proliferation, and that inhibition of the activity of GAPDH significantly limits T-cell activation and proliferation and extends the survival of hVAV1-MYO1F knock-in mice.

重要的是，我们发现VAV1-MYO1F（一种复发性外周T细胞淋巴瘤（PTCL）相关致癌蛋白）的融合蛋白促进GAPDH的过度乙酰化及其活化，从而导致异常的糖酵解和T细胞增殖，并且抑制GAPDH的活性显着限制了T细胞的活化和增殖，并延长了hVAV1-MYO1F敲入小鼠的存活。

Moreover, hyperacetylation of GAPDH was confirmed in human PTCL patient samples containing the VAV1-MYO1F gene fusion. Overall, this study revealed not only the mechanisms by which MYO1F regulates T-cell metabolism and VAV1-MYO1F fusion-induced PTCL but also promising therapeutic targets for the treatment of PTCL..

此外，在含有VAV1-MYO1F基因融合的人PTCL患者样品中证实了GAPDH的高度乙酰化。总体而言，这项研究不仅揭示了MYO1F调节T细胞代谢和VAV1-MYO1F融合诱导的PTCL的机制，而且还揭示了治疗PTCL的有希望的治疗靶点。。

Access through your institution

通过您的机构访问

Buy or subscribe

购买或订阅

This is a preview of subscription content, access via your institution

这是订阅内容的预览，可通过您的机构访问

Access options

访问选项

Access through your institution

通过您的机构访问

Access through your institution

通过您的机构访问

Change institution

变革机构

Buy or subscribe

购买或订阅

Subscribe to this journal

订阅此日记

Receive 12 digital issues and online access to articles

接收12期数字期刊并在线访问文章

111,21 € per year

每年111,21欧元

only 9,27 € per issue

每期仅9.27欧元

Learn more

了解更多信息

Buy this article

购买这篇文章

Purchase on SpringerLink

在SpringerLink上购买

Instant access to full article PDF

即时访问全文PDF

Buy now

立即购买

Prices may be subject to local taxes which are calculated during checkout

价格可能需要缴纳结帐时计算的地方税

Additional access options:

其他访问选项：

Log in

登录

Learn about institutional subscriptions

了解机构订阅

Read our FAQs

阅读我们的常见问题

Contact customer support

联系客户支持

Fig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6Fig. 7

图1图。图2。3图。4图。5图。6图。7

ReferencesBantug GR, et al. The spectrum of T-cell metabolism in health and disease. Nat Rev Immunol. 2018;18:19–34.Article

参考Bantug GR等人，健康和疾病中T细胞代谢的光谱。Nat Rev免疫。2018年；18： 19-34.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Finlay D, Cantrell DA. Metabolism, migration and memory in cytotoxic T cells. Nat Rev Immunol. 2011;11:109–17.Article

Finlay D，Cantrell DA。细胞毒性T细胞的代谢，迁移和记忆。Nat Rev免疫。2011年；11： 109-17.条款

CAS

中科院

PubMed

PubMed

PubMed Central

PubMed 中心

Google Scholar

谷歌学者

Geltink RIK, et al. Unraveling the complex interplay between T-cell metabolism and function. Annu Rev Immunol. 2018;36:461–88.Article

Geltink RIK等人揭示了T细胞代谢和功能之间复杂的相互作用。Annu Rev免疫。2018年；36:461-88.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

O’Sullivan D, Pearce EL. Targeting T-cell metabolism for therapy. Trends Immunol. 2015;36:71–80.Article

O'Sullivan D，Pearce EL。针对T细胞代谢进行治疗。趋势免疫。2015年；36:71–80.文章

PubMed

PubMed

PubMed Central

PubMed 中心

Google Scholar

谷歌学者

Reina-Campos M, et al. CD8(+) T-cell metabolism in infection and cancer. Nat Rev Immunol. 2021;21:718–38.Article

Reina Campos M等人。感染和癌症中的CD8（+）T细胞代谢。Nat Rev免疫。2021年；21:718–38.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Chapman NM, et al. Metabolic coordination of T-cell quiescence and activation. Nat Rev Immunol. 2020;20:55–70.Article

Chapman NM等人。T细胞静止和活化的代谢协调。Nat Rev免疫。2020年；20：

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

O’Neill LA, et al. A guide to immunometabolism for immunologists. Nat Rev Immunol. 2016;16:553–65.Article

O'Neill LA等人，《免疫学家免疫代谢指南》。Nat Rev免疫。2016年；16： 553-65.条

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Pearce EL, et al. Fueling immunity: insights into metabolism and lymphocyte function. Science. 2013;342:1242454.Article

Pearce EL等人，《增强免疫力：对新陈代谢和淋巴细胞功能的见解》。科学。2013年；342:1242454.文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

MacIver NJ, et al. Metabolic regulation of T lymphocytes. Annu Rev Immunol. 2013;31:259–83.Article

MacIver NJ等人。T淋巴细胞的代谢调节。Annu Rev免疫。2013年；31:259–83.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Shyer JA, et al. Metabolic signaling in T cells. Cell Res. 2020;30:649–59.Article

Shyer JA等人。T细胞中的代谢信号传导。Cell Res.2020；30:649–59.文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Chi H. Regulation and function of mTOR signaling in T-cell fate decisions. Nat Rev Immunol. 2012;12:325–38.Article

Chi H.mTOR信号在T细胞命运决定中的调节和功能。Nat Rev免疫。2012年；12： 325-38.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Delgoffe GM, et al. The kinase mTOR regulates the differentiation of helper T cells through the selective activation of signaling by mTORC1 and mTORC2. Nat Immunol. 2011;12:295–303.Article

激酶mTOR通过mTORC1和mTORC2选择性激活信号传导来调节辅助性T细胞的分化。Nat免疫。2011年；12： 295-303.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Rao RR, et al. The mTOR kinase determines effector versus memory CD8+ T-cell fate by regulating the expression of transcription factors T-bet and Eomesodermin. Immunity. 2010;32:67–78.Article

mTOR激酶通过调节转录因子T-bet和Eomesodermin的表达来决定效应子与记忆CD8+T细胞的命运。豁免。2010年；32:67–78.文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Ray JP, et al. The Interleukin-2-mTORc1 Kinase axis defines the signaling, differentiation, and metabolism of T Helper 1 and follicular B helper T cells. Immunity. 2015;43:690–702.Article

白细胞介素-2-mTORc1激酶轴定义了T辅助细胞1和滤泡B辅助T细胞的信号传导，分化和代谢。豁免。2015年；43:690–702.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Verbist KC, et al. Metabolic maintenance of cell asymmetry following division in activated T lymphocytes. Nature. 2016;532:389–93.Article

Verbist KC等人。活化T淋巴细胞分裂后细胞不对称的代谢维持。自然。2016年；532:389–93.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Blagih J, et al. The energy sensor AMPK regulates T-cell metabolic adaptation and effector responses in vivo. Immunity. 2015;42:41–54.Article

能量传感器AMPK在体内调节T细胞代谢适应和效应反应。豁免。2015年；42:41–54.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Dang EV, et al. Control of T(H)17/T(reg) balance by hypoxia-inducible factor 1. Cell. 2011;146:772–84.Article

Dang EV等人。通过缺氧诱导因子1控制T（H）17/T（reg）平衡。细胞。2011年；146:772-84.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Shi LZ, et al. HIF1alpha-dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells. J Exp Med. 2011;208:1367–76.Article

Shi LZ等人。HIF1α依赖性糖酵解途径协调了TH17和Treg细胞分化的代谢检查点。J Exp Med。2011；208:1367–76.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Yang JQ, et al. RhoA orchestrates glycolysis for TH2 cell differentiation and allergic airway inflammation. J Allergy Clin Immunol. 2016;137:231–45 e234.Article

Yang JQ等人。RhoA协调TH2细胞分化和过敏性气道炎症的糖酵解。J过敏临床免疫。2016年；137:231–45 e234。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Kishton RJ, et al. AMPK is essential to balance glycolysis and mitochondrial metabolism to control T-ALL cell stress and survival. Cell Metab. 2016;23:649–62.Article

AMPK对于平衡糖酵解和线粒体代谢以控制T-ALL细胞应激和存活至关重要。细胞代谢。2016年；23:649–62.文章

CAS

中科院

PubMed

PubMed

PubMed Central

PubMed 中心

Google Scholar

谷歌学者

Elia I, et al. Tumor cells dictate anti-tumor immune responses by altering pyruvate utilization and succinate signaling in CD8(+) T cells. Cell Metab. 2022;34:1137–50 e1136.Article

肿瘤细胞通过改变CD8（+）T细胞中丙酮酸的利用和琥珀酸信号传导来决定抗肿瘤免疫反应。细胞代谢。2022年；34:1137–50 e1136。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Fischer K, et al. Inhibitory effect of tumor cell-derived lactic acid on human T cells. Blood. 2007;109:3812–9.Article

Fischer K等人。肿瘤细胞衍生的乳酸对人T细胞的抑制作用。血。2007年；109:3812-9.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Macintyre AN, et al. The glucose transporter Glut1 is selectively essential for CD4 T-cell activation and effector function. Cell Metab. 2014;20:61–72.Article

葡萄糖转运蛋白Glut1对于CD4 T细胞活化和效应功能是选择性必需的。细胞代谢。2014年；20： 61-72.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Piotrowski JT, et al. WASH knockout T cells demonstrate defective receptor trafficking, proliferation, and effector function. Mol Cell Biol. 2013;33:958–73.Article

Piotrowski JT等人，WASH基因敲除T细胞表现出受体运输，增殖和效应功能缺陷。摩尔细胞生物学。2013年；33:958–73.文章

CAS

中科院

PubMed

PubMed

PubMed Central

PubMed 中心

Google Scholar

谷歌学者

Berod L, et al. De novo fatty acid synthesis controls the fate between regulatory T and T helper 17 cells. Nat Med. 2014;20:1327–33.Article

从头脂肪酸合成控制调节性T细胞和T辅助细胞17之间的命运。Nat Med。2014；20： 1327-33.条

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Galluzzi L, et al. Metabolic targets for cancer therapy. Nat Rev Drug Discov. 2013;12:829–46.Article

Galluzzi L等人。癌症治疗的代谢靶标。。2013年；12： 829-46.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Kroemer G, Pouyssegur J. Tumor cell metabolism: cancer’s Achilles’ heel. Cancer Cell. 2008;13:472–82.Article

Kroemer G，Pouyssegur J.肿瘤细胞代谢：癌症的致命弱点。癌细胞。2008年；13： 472-82.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Chang CH, et al. Posttranscriptional control of T-cell effector function by aerobic glycolysis. Cell. 2013;153:1239–51.Article

Chang CH等人。通过有氧糖酵解对T细胞效应子功能的转录后控制。细胞。2013年；153:1239-51.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Colell A, et al. GAPDH and autophagy preserve survival after apoptotic cytochrome c release in the absence of caspase activation. Cell. 2007;129:983–97.Article

Colell A等人。在没有半胱天冬酶活化的情况下，GAPDH和自噬在凋亡细胞色素c释放后保持存活。细胞。2007年；129:983–97.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Liberti MV, et al. A predictive model for selective targeting of the warburg effect through GAPDH inhibition with a natural product. Cell Metab. 2017;26:648–659 e648.Article

Liberti MV等人。通过天然产物抑制GAPDH选择性靶向warburg效应的预测模型。细胞代谢。2017年；26:648–659 e648。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Colell A, et al. Novel roles for GAPDH in cell death and carcinogenesis. Cell Death Differ. 2009;16:1573–81.Article

Colell A等人。GAPDH在细胞死亡和致癌作用中的新作用。细胞死亡不同。2009年；16： 1573-81.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Balmer ML, et al. Memory CD8(+) T cells require increased concentrations of acetate induced by stress for optimal function. Immunity. 2016;44:1312–24.Article

Balmer ML等人。记忆CD8（+）T细胞需要增加应激诱导的乙酸盐浓度才能获得最佳功能。豁免。2016年；44:1312–24.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Xu Y, et al. Glycolysis determines dichotomous regulation of T-cell subsets in hypoxia. J Clin Invest. 2016;126:2678–88.Article

Xu Y等人。糖酵解决定缺氧时T细胞亚群的二分调节。J临床投资。2016年；126:2678–88.文章

PubMed

PubMed

PubMed Central

PubMed 中心

Google Scholar

谷歌学者

Gubser PM, et al. Rapid effector function of memory CD8+ T cells requires an immediate-early glycolytic switch. Nat Immunol. 2013;14:1064–72.Article

记忆CD8+T细胞的快速效应功能需要立即进行早期糖酵解转换。Nat免疫。2013年；14： 1064-72.条

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Mondragon L, et al. GAPDH overexpression in the T-cell lineage promotes angioimmunoblastic T-cell Lymphoma through an NF-kappaB-dependent mechanism. Cancer Cell. 2019;36:268–87 e210.Article

T细胞谱系中的GAPDH过表达通过NF-κB依赖性机制促进血管免疫母细胞性T细胞淋巴瘤。癌细胞。2019年；36:268–87 e210。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Barger SR, et al. Membrane-cytoskeletal crosstalk mediated by myosin-I regulates adhesion turnover during phagocytosis. Nat Commun. 2019;10:1249.Article

由肌球蛋白-I介导的膜细胞骨架串扰调节吞噬过程中的粘附转换。纳特公社。2019年；10： 第1249条

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Kim SV, et al. Modulation of cell adhesion and motility in the immune system by Myo1f. Science. 2006;314:136–9.Article

。科学。2006年；314:136–9.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Salvermoser M, et al. Myosin 1f is specifically required for neutrophil migration in 3D environments during acute inflammation. Blood. 2018;131:1887–98.Article

Salvermoser M等人。在急性炎症期间，中性粒细胞在3D环境中迁移特别需要肌球蛋白1f。血。2018年；131:1887–98.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Sun W, et al. MYO1F regulates antifungal immunity by regulating acetylation of microtubules. Proc Natl Acad Sci USA. 2021;118:e2100230118.Article

Sun W等人。MYO1F通过调节微管的乙酰化来调节抗真菌免疫。美国国家科学院院刊2021；118:e2100230118.文章

CAS

中科院

PubMed

PubMed

PubMed Central

PubMed 中心

Google Scholar

谷歌学者

Jerby-Arnon L, et al. A cancer cell program promotes T-cell exclusion and resistance to checkpoint blockade. Cell. 2018;175:984–97 e924.Article

Jerby Arnon L等人。癌细胞计划促进T细胞排斥和对检查点封锁的抵抗。细胞。2018年；

CAS

中科院

PubMed

PubMed

PubMed Central

PubMed 中心

Google Scholar

谷歌学者

Song WM, et al. Network models of primary melanoma microenvironments identify key melanoma regulators underlying prognosis. Nat Commun. 2021;12:1214.Article

Song WM等人。原发性黑色素瘤微环境的网络模型确定了潜在预后的关键黑色素瘤调节剂。纳特公社。2021年；12： 第1214条

CAS

中科院

PubMed

PubMed

PubMed Central

PubMed 中心

Google Scholar

谷歌学者

Abate F, et al. Activating mutations and translocations in the guanine exchange factor VAV1 in peripheral T-cell lymphomas. Proc Natl Acad Sci USA. 2017;114:764–9.Article

Abate F等人。激活外周T细胞淋巴瘤中鸟嘌呤交换因子VAV1的突变和易位。美国国家科学院院刊2017；114:764–9.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Cortes JR, et al. Oncogenic Vav1-Myo1f induces therapeutically targetable macrophage-rich tumor microenvironment in peripheral T-cell lymphoma. Cell Rep. 2022;39:110695.Article

Cortes JR等人。致癌Vav1-Myo1f在外周T细胞淋巴瘤中诱导可治疗靶向的富含巨噬细胞的肿瘤微环境。细胞代表2022；39:110695.文章

CAS

中科院

PubMed

PubMed

PubMed Central

PubMed 中心

Google Scholar

谷歌学者

Morrish E, et al. The fusion oncogene VAV1-MYO1F triggers aberrant T-cell receptor signaling in vivo and drives peripheral T-cell lymphoma in mice. Eur J Immunol. 2023;53:e2250147.Article

融合癌基因VAV1-MYO1F在体内触发异常的T细胞受体信号传导，并驱动小鼠外周T细胞淋巴瘤。欧洲免疫杂志。2023年；53:e2250147.文章

PubMed

PubMed

Google Scholar

谷歌学者

Panagopoulos I, et al. Germline MYOF1::WNK4 and VPS25::MYOF1 chimeras generated by the constitutional translocation t(17;19)(q21;p13) in two siblings with Myelodysplastic Syndrome. Cancer Genomics Proteom. 2024;21:272–84.Article

Panagopoulos I等人。由两个患有骨髓增生异常综合征的兄弟姐妹的体质易位t（17；19）（q21；p13）产生的种系MYOF1：：WNK4和VPS25：：MYOF1嵌合体。癌症基因组学蛋白质组学。2024年；21:272–84.文章

CAS

中科院

Google Scholar

谷歌学者

Kuchroo VK, et al. T-cell response in experimental autoimmune encephalomyelitis (EAE): role of self and cross-reactive antigens in shaping, tuning, and regulating the autopathogenic T-cell repertoire. Annu Rev Immunol. 2002;20:101–23.Article

Kuchroo VK等人。实验性自身免疫性脑脊髓炎（EAE）中的T细胞反应：自身和交叉反应抗原在形成，调节和调节自身致病性T细胞库中的作用。Annu Rev免疫。2002年；20： 101-23.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Chen J, et al. TAGAP instructs Th17 differentiation by bridging Dectin activation to EPHB2 signaling in innate antifungal response. Nat Commun. 2020;11:1913.Article

TAGAP通过在先天性抗真菌反应中将Dectin激活桥接到EPHB2信号传导来指导Th17分化。纳特公社。2020年；11： 1913年

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Abramson J, et al. Accurate structure prediction of biomolecular interactions with AlphaFold 3. Nature. 2024;630:493–500.Choi W, et al. Efficient tagging of endogenous proteins in human cell lines for structural studies by single-particle cryo-EM. Proc Natl Acad Sci USA. 2023;120:e2302471120.Article .

Abramson J等人。生物分子与α折叠3相互作用的精确结构预测。自然。2024年；630:493–500.Choi W等人。通过单颗粒冷冻电镜对人类细胞系中内源性蛋白质进行有效标记以进行结构研究。美国国家科学院院刊，2023年；120:e2302471120。文章。

CAS

中科院

PubMed

PubMed

PubMed Central

PubMed 中心

Google Scholar

谷歌学者

Menk AV, et al. Early TCR signaling induces rapid aerobic glycolysis enabling distinct acute T-cell effector functions. Cell Rep. 2018;22:1509–21.Article

早期TCR信号传导诱导快速有氧糖酵解，从而实现不同的急性T细胞效应功能。细胞代表2018；22:1509–21.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Frauwirth KA, et al. The CD28 signaling pathway regulates glucose metabolism. Immunity. 2002;16:769–77.Article

Frauwirth KA等人。CD28信号通路调节葡萄糖代谢。豁免。2002年；16： 769-77.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Wei Q, et al. Lck bound to coreceptor is less active than free Lck. Proc Natl Acad Sci USA. 2020;117:15809–17.Article

Wei Q等人。与辅受体结合的Lck活性低于游离Lck。美国国家科学院院刊2020；117:15809–17.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Moldovan MC, et al. CD4 dimers constitute the functional component required for T-cell activation. J Immunol. 2002;169:6261–8.Article

摩尔多瓦MC等人。CD4二聚体构成T细胞活化所需的功能成分。免疫杂志。2002年；169:6261–8.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Holdorf AD, et al. Regulation of Lck activity by CD4 and CD28 in the immunological synapse. Nat Immunol. 2002;3:259–64.Article

Holdorf AD等人。免疫突触中CD4和CD28对Lck活性的调节。Nat免疫。2002年；3： 259-64.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Nolz JC, et al. TCR/CD28-stimulated actin dynamics are required for NFAT1-mediated transcription of c-rel leading to CD28 response element activation. J Immunol. 2007;179:1104–12.Article

NFAT1介导的c-rel转录导致CD28反应元件激活需要TCR/CD28刺激的肌动蛋白动力学。免疫杂志。2007年；179:1104-12.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Bunnell SC, et al. Dynamic Actin polymerization drives T-cell receptor–induced spreading: a role for the signal transduction adaptor LAT. Immunity. 2001;14:315–29.Article

。2001年；14： 315-29.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Krendel M, Mooseker MS. Myosins: Tails (and Heads) of functional diversity. Physiology 2005;20:239–51.Article

Krendel M，Mooseker女士肌球蛋白：功能多样性的尾巴（和头部）。生理学2005；20： 239-51.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Foss FM, et al. Peripheral T-cell lymphoma. Blood. 2011;117:6756–67.Article

Foss FM等。外周T细胞淋巴瘤。血。2011年；117:6756–67.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Boddicker RL, et al. Integrated mate-pair and RNA sequencing identifies novel, targetable gene fusions in peripheral T-cell lymphoma. Blood. 2016;128:1234–45.Article

Boddicker RL等人。整合配对和RNA测序鉴定外周T细胞淋巴瘤中新的可靶向基因融合。血。2016年；128:1234-45.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Tybulewicz VL. Vav-family proteins in T-cell signaling. Curr Opin Immunol. 2005;17:267–74.Article

Tybulewicz公司。T细胞信号传导中的Vav家族蛋白。Curr Opin免疫。2005年；17： 267-74.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Tybulewicz VL, et al. Vav1: a key signal transducer downstream of the TCR. Immunol Rev. 2003;192:42–52.Article

Tybulewicz VL等人。Vav1：TCR下游的关键信号传感器。免疫修订版2003；192:42-52.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Wang X, et al. A GAPDH serotonylation system couples CD8(+) T-cell glycolytic metabolism to antitumor immunity. Mol Cell. 2024;84:760–75 e767.Article

GAPDH血清素化系统将CD8（+）T细胞糖酵解代谢与抗肿瘤免疫结合起来。摩尔细胞。2024年；84:760–75 e767。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Chang C, et al. AMPK-dependent phosphorylation of GAPDH triggers Sirt1 activation and is necessary for autophagy upon glucose starvation. Mol Cell. 2015;60:930–40.Article

Chang C等人。GAPDH的AMPK依赖性磷酸化触发Sirt1激活，并且是葡萄糖饥饿时自噬所必需的。摩尔细胞。2015年；60:930–40.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Sun Young L, et al. Glyceraldehyde-3-Phosphate, a glycolytic intermediate, prevents cells from apoptosis by lowering S-Nitrosylation of Glyceraldehyde-3-Phosphate Dehydrogenase. J Microbiol Biotechnol 2012;22:571–3.Article

。J Microbiol Biotechnol 2012；22:571–3.文章

Google Scholar

谷歌学者

Hara MR, Snyder SH. Nitric oxide–GAPDH–Siah: A novel cell death cascade. Cell Mol Neurobiol. 2006;26:525–36.Article

Hara MR，Snyder SH。一氧化氮–GAPDH–Siah：一种新型的细胞死亡级联反应。细胞摩尔神经生物学。2006年；26:525–36.文章

Google Scholar

谷歌学者

Ventura M, et al. Nuclear translocation of glyceraldehyde-3-phosphate dehydrogenase is regulated by acetylation. Int J Biochem Cell Biol. 2010;42:1672–80.Article

Ventura M等人。甘油醛-3-磷酸脱氢酶的核转位受乙酰化调节。Int J生物化学细胞生物学。2010年；42:1672-80.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Ganapathy-Kanniappan S. Evolution of GAPDH as a druggable target of tumor glycolysis? Expert Opin Ther Targets. 2018;22:295–8.Article

Ganapathy Kanniappan S.GAPDH作为肿瘤糖酵解药物靶标的进化？专家意见其他目标。2018年；22:295–8.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Yun J, et al. Vitamin C selectively kills KRAS and BRAF mutant colorectal cancer cells by targeting GAPDH. Science. 2015;350:1391–6.Article

。科学。2015年；350:1391–6.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Liberti MV, et al. Evolved resistance to partial GAPDH inhibition results in loss of the Warburg effect and in a different state of glycolysis. J Biol Chem. 2020;295:111–24.Article

Liberti MV等人。对部分GAPDH抑制的进化抗性导致Warburg效应的丧失和糖酵解的不同状态。生物化学杂志。2020年；295:111-24.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Download referencesAcknowledgementsThis investigation was supported by grants from the National Science Fund for Distinguished Young Scholars (82225029, to C.H.W.); the Youth Fund of the National Natural Science Foundation of China (82302628, to Y.Y.D., 82301989, to R.R.H., 82301987 to B.Z.

下载参考文献致谢这项调查得到了国家杰出青年科学基金（82225029，授予C.H.W.）的资助；国家自然科学基金青年基金（82302628，至Y.Y.D.，82301989，至R.R.H.，82301987至B.Z。

and 82402704 to Y.Y.L.); the Original Exploration Program of the National Natural Science Foundation of China (82150102, to C.H.W.); the National Key Research and Development Program of China (2020YFA0710700, to C.H.W.); the Postdoctoral Foundation of China (2022M720658, to Y.Y.D., and 2022M720659 to R.R.H.); the Sichuan Postdoctoral Innovation Plan (BX202202, to Y.Y.D.); the Postdoctoral Foundation of Sichuan Provincial People’s Hospital (2022BH01, to R.R.H.

和Y.Y.L.的82402704）；国家自然科学基金原始探索计划（82150102，致C.H.W.）；中国国家重点研究发展计划（2020YFA0710700，致C.H.W.）；中国博士后基金会（2022M720658，授予Y.Y.D.，2022M720659授予R.R.H.）；四川博士后创新计划（BX202202，致Y.Y.D.）；四川省人民医院博士后基金会（2022BH01，R.R.H。

and 2022BH07, to M.Y.); and the Postdoctoral Foundation of Sichuan Province (TB2022086, to R.R.H., TB2023092, to L.Y.F.).Author informationAuthor notesThese authors contributed equally: Zhihui Cui, Heping Wang.Authors and AffiliationsKey Laboratory of Molecular Biophysics of the Ministry of Education, National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074; Key Laboratory for Human Disease Gene Study of Sichuan Province and the Department of Laboratory Medicine, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, ChinaZhihui Cui, Heping Wang, Xiong Feng & Ru GaoThe Key Laboratory for Human Disease Gene Study of Sichuan Province and the Department of Laboratory Medicine, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, ChinaChuyu Wu, Ming Yi, Ruirui He, Lingyun Feng, Bo Zeng, Yanyun Du & Chenhui WangResearch U.

和2022BH07，M.Y.）；和四川省博士后基金会（TB2022086，致R.R.H.，TB2023092，致L.Y.F.）。。作者和附属机构教育部分子生物物理学实验室，华中科技大学生命科学与技术学院国家纳米医学工程研究中心，武汉430074；四川省人类疾病基因研究重点实验室和中国电子科技大学四川省人民医院检验医学系，成都，中国崔志辉，王和平，熊峰和如高四川省人类疾病基因研究重点实验室和中国电子科技大学四川省人民医院检验医学系，成都，中国吴楚瑜，明毅，何瑞瑞，冯凌云，曾波，杜艳云和王晨辉。

PubMed Google ScholarHeping WangView author publicationsYou can also search for this author in

PubMed Google ScholarHeping WangView作者出版物您也可以在

PubMed Google ScholarXiong FengView author publicationsYou can also search for this author in

PubMed Google ScholarXiong FengView作者出版物您也可以在

PubMed Google ScholarChuyu WuView author publicationsYou can also search for this author in

PubMed Google ScholarChuyu WuView作者出版物您也可以在

PubMed Google ScholarMing YiView author publicationsYou can also search for this author in

PubMed谷歌学术评论作者出版物您也可以在

PubMed Google ScholarRuirui HeView author publicationsYou can also search for this author in

PubMed谷歌学术评论HeView作者出版物您也可以在

PubMed Google ScholarTing PanView author publicationsYou can also search for this author in

PubMed Google ScholarTing PanView作者出版物您也可以在

PubMed Google ScholarRu GaoView author publicationsYou can also search for this author in

PubMed Google ScholarRu GaoView作者出版物您也可以在

PubMed Google ScholarLingyun FengView author publicationsYou can also search for this author in

PubMed Google ScholarLingyun FengView作者出版物您也可以在

PubMed Google ScholarBo ZengView author publicationsYou can also search for this author in

PubMed Google ScholarGuoling HuangView author publicationsYou can also search for this author in

PubMed Google Scholargouling HuangView作者出版物您也可以在

PubMed Google ScholarYuan WangView author publicationsYou can also search for this author in

PubMed Google ScholarYuan WangView作者出版物您也可以在

PubMed Google ScholarYanyun DuView author publicationsYou can also search for this author in

PubMed Google ScholarYanyun DuView作者出版物您也可以在

PubMed Google ScholarCun-jin ZhangView author publicationsYou can also search for this author in

PubMed Google ScholarCun jin ZhangView作者出版物您也可以在

PubMed Google ScholarXue XiaoView author publicationsYou can also search for this author in

PubMed Google ScholarXue XiaoView作者出版物您也可以在

PubMed Google ScholarChenhui WangView author publicationsYou can also search for this author in

PubMed Google ScholarChenhui WangView作者出版物您也可以在

PubMed Google ScholarContributionsZHC and HPW performed the experiments with the assistance of XF, YYD, MY, RRH, TP, RG, LYF, BZ, GLH, and YW; CYW, and CJZ helped to perform the EAE experiments; XX helped to obtain the human PTCL samples and scored the acetylation level of GAPDH in the samples.

PubMed Google ScholarContributionsZHC和HPW在XF，YYD，MY，RRH，TP，RG，LYF，BZ，GLH和YW的帮助下进行了实验；CYW和CJZ帮助进行了EAE实验；XX帮助获得了人PTCL样品，并对样品中GAPDH的乙酰化水平进行了评分。

ZHC and CHW designed the experiments and analyzed the data; CHW wrote the manuscript and supervised the project with YYD, CJZ, and XX.Corresponding authorsCorrespondence to.

ZHC和CHW设计了实验并分析了数据；CHW撰写了手稿，并与YYD，CJZ和XX一起监督了该项目。通讯作者通讯。

Yanyun Du, Cun-jin Zhang, Xue Xiao or Chenhui Wang.Ethics declarations

杜艳云、张存金、薛晓或王晨辉。道德宣言

Competing interests

相互竞争的利益

The authors declare no competing interests.

作者声明没有利益冲突。

Supplementary informationFigures 1-6 and supplementary Figure 4-6 of the original image.pdfSupplementary Figure 1Supplementary Figure 2Supplementary Figure 3Supplementary Figure 4Supplementary Figure 5Supplementary Figure 6Supplementary Figure 7Supplementary Figure LegendsRights and permissionsSpringer Nature or its licensor (e.g.

补充信息原始图像的图1-6和补充图4-6.PDF补充图1补充图2补充图3补充图4补充图5补充图6补充图7补充图LegendsRights and PermissionsPringer Nature或其许可人（例如。

a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.Reprints and permissionsAbout this articleCite this articleCui, Z., Wang, H., Feng, X.

协会或其他合作伙伴）根据与作者或其他权利持有人的出版协议对本文拥有专有权；本文接受稿件版本的作者自行存档仅受此类出版协议和适用法律的条款管辖。转载和许可本文引用本文Cui，Z.，Wang，H.，Feng，X。

et al. MYO1F regulates T-cell activation and glycolytic metabolism by promoting the acetylation of GAPDH..

MYO1F通过促进GAPDH的乙酰化来调节T细胞活化和糖酵解代谢。。

Cell Mol Immunol (2024). https://doi.org/10.1038/s41423-024-01247-6Download citationReceived: 05 September 2024Accepted: 27 November 2024Published: 13 December 2024DOI: https://doi.org/10.1038/s41423-024-01247-6Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard.

细胞摩尔免疫（2024）。https://doi.org/10.1038/s41423-024-01247-6Download引文收到日期：2024年9月5日接受日期：2024年11月27日发布日期：2024年12月13日OI：https://doi.org/10.1038/s41423-024-01247-6Share本文与您共享以下链接的任何人都可以阅读此内容：获取可共享链接对不起，本文目前没有可共享的链接。复制到剪贴板。

Provided by the Springer Nature SharedIt content-sharing initiative

由Springer Nature SharedIt内容共享计划提供

KeywordsT cell activationMYO1FGAPDHVAV1-MYO1F fusionPeripheral T-cell lymphoma (PTCL)

关键词ST细胞活化MYO1FGAPDHVAV1-MYO1F融合外周T细胞淋巴瘤（PTCL）