AbstractThe T cell Ubiquitin Ligand (TULA) protein family contains two members, UBASH3A and UBASH3B, that display similarities in protein sequence and domain structure. Both TULA proteins act to repress T cell activation via a combination of overlapping and nonredundant functions. UBASH3B acts mainly as a phosphatase that suppresses proximal T cell receptor (TCR) signaling.

摘要T细胞泛素配体（TULA）蛋白家族包含两个成员，UBASH3A和UBASH3B，它们在蛋白质序列和结构域结构上显示出相似性。。UBASH3B主要作为抑制近端T细胞受体（TCR）信号传导的磷酸酶。

In contrast, UBASH3A acts primarily as an adaptor protein, interacting with other proteins (including UBASH3B) in T cells upon TCR stimulation and resulting in downregulation of TCR signaling and NF-κB signaling. Human genetic and functional studies have revealed another notable distinction between UBASH3A and UBASH3B: numerous genome-wide association studies have identified statistically significant associations between genetic variants in and around the UBASH3A gene and at least seven different autoimmune diseases, suggesting a key role of UBASH3A in autoimmunity.

相反，UBASH3A主要作为衔接蛋白，在TCR刺激后与T细胞中的其他蛋白（包括UBASH3B）相互作用，导致TCR信号传导和NF-κB信号传导下调。人类遗传和功能研究揭示了UBASH3A和UBASH3B之间的另一个显着区别：许多全基因组关联研究已经确定了UBASH3A基因及其周围的遗传变异与至少七种不同的自身免疫性疾病之间的统计学显着关联，表明UBASH3A在自身免疫中的关键作用。

However, the evidence for an independent role of UBASH3B in autoimmune disease is limited. This review summarizes key findings regarding the roles of TULA proteins in T cell biology and autoimmunity, highlights the commonalities and differences between UBASH3A and UBASH3B, and speculates on the individual and joint effects of TULA proteins on T cell signaling..

然而，UBASH3B在自身免疫性疾病中独立作用的证据是有限的。本综述总结了关于TULA蛋白在T细胞生物学和自身免疫中的作用的关键发现，强调了UBASH3A和UBASH3B之间的共性和差异，并推测了TULA蛋白对T细胞信号传导的个体和联合作用。。

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Fig. 1: Domains of human UBASH3A and UBASH3B.Fig. 2: Binding partners of human UBASH3A and UBASH3B.Fig. 3: Proposed models for UBASH3A regulation of the IκB kinase (IKK) complex.

图1：人UBASH3A和UBASH3B的结构域。图2：人UBASH3A和UBASH3B的结合伴侣。图3:UBASH3A调节IκB激酶（IKK）复合物的拟议模型。

ReferencesTsygankov AY. TULA proteins in men, mice, hens, and lice: welcome to the family. Int J Mol Sci. 2023;24:9126.Article

参考文献Sygankov AY。男性，小鼠，母鸡和虱子中的TULA蛋白：欢迎来到这个家庭。。2023年；24:9126.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Nicolas P, Ollier J, Mori D, Voisinne G, Celis-Gutierrez J, Gregoire C, et al. Systems-level conservation of the proximal TCR signaling network of mice and humans. J Exp Med. 2022;219:e20211295.Article

Nicolas P，Ollier J，Mori D，Voisinne G，Celis Gutierrez J，Gregoire C等。小鼠和人类近端TCR信号网络的系统级保护。J Exp Med。2022；219:e20211295.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Ge Y, Paisie TK, Newman JRB, McIntyre LM, Concannon P. UBASH3A mediates risk for type 1 diabetes through inhibition of T-cell receptor-induced NF-κB signaling. Diabetes. 2017;66:2033–43.Article

Ge Y，Paisie TK，Newman JRB，McIntyre LM，Concannon P.UBASH3A通过抑制T细胞受体诱导的NF-κB信号传导介导1型糖尿病的风险。糖尿病。2017年；66:2033–43.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Carpino N, Turner S, Mekala D, Takahashi Y, Zang H, Geiger TL, et al. Regulation of ZAP-70 activation and TCR signaling by two related proteins, Sts-1 and Sts-2. Immunity. 2004;20:37–46.Article

Carpino N，Turner S，Mekala D，Takahashi Y，Zang H，Geiger TL等。两种相关蛋白Sts-1和Sts-2对ZAP-70活化和TCR信号传导的调节。豁免。；20： 37-46.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Mori D, Grégoire C, Voisinne G, Celis-Gutierrez J, Aussel R, Girard L, et al. The T cell CD6 receptor operates a multitask signalosome with opposite functions in T cell activation. J Exp Med. 2021;218:e20201011.Article

Mori D，Grégoire C，Voisinne G，Celis Gutierrez J，Aussel R，Girard L等。T细胞CD6受体操作多任务信号体，在T细胞活化中具有相反的功能。J Exp Med。2021；218:e20201011.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Voisinne G, Locard-Paulet M, Froment C, Maturin E, Menoita MG, Girard L, et al. Kinetic proofreading through the multi-step activation of the ZAP70 kinase underlies early T cell ligand discrimination. Nat Immunol. 2022;23:1355–64.Article

Voisinne G，Locard Paulet M，Froment C，Maturin E，Menoita MG，Girard L等。通过ZAP70激酶的多步激活进行动力学校对是早期T细胞配体区分的基础。Nat免疫。2022年；23:1355–64.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Feshchenko EA, Smirnova EV, Swaminathan G, Teckchandani AM, Agrawal R, Band H, et al. TULA: an SH3- and UBA-containing protein that binds to c-Cbl and ubiquitin. Oncogene. 2004;23:4690–706.Article

Feshchenko EA，Smirnova EV，Swaminathan G，Teckhandani AM，Agrawal R，Band H等。TULA：一种含有SH3和UBA的蛋白质，与c-Cbl和泛素结合。致癌基因。；23:4690–706.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Kowanetz K, Crosetto N, Haglund K, Schmidt M, Heldin C-H, Dikic I. Suppressors of T-cell receptor signaling Sts-1 and Sts-2 bind to Cbl and inhibit endocytosis of receptor tyrosine kinases. J Biol Chem. 2004;279:32786–95.Article

Kowanetz K，Crosetto N，Haglund K，Schmidt M，Heldin C-H，Dikic I.T细胞受体信号转导抑制剂Sts-1和Sts-2与Cbl结合并抑制受体酪氨酸激酶的内吞作用。生物化学杂志。；279:32786–95.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Hoeller D, Crosetto N, Blagoev B, Raiborg C, Tikkanen R, Wagner S, et al. Regulation of ubiquitin-binding proteins by monoubiquitination. Nat Cell Biol. 2006;8:163–9.Article

Hoeller D，Crosetto N，Blagoev B，Raiborg C，Tikkanen R，Wagner S等。通过单泛素化调节泛素结合蛋白。Nat细胞生物学。2006年；8： 163-9.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Carpino N, Chen Y, Nassar N, Oh H-W. The Sts proteins target tyrosine phosphorylated, ubiquitinated proteins within TCR signaling pathways. Mol Immunol. 2009;46:3224–31.Article

Carpino N，Chen Y，Nassar N，Oh H-W。Sts蛋白靶向TCR信号通路中酪氨酸磷酸化的泛素化蛋白。摩尔免疫。2009年；46:3224–31.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Krupina K, Kleiss C, Metzger T, Fournane S, Schmucker S, Hofmann K, et al. Ubiquitin receptor protein UBASH3B drives aurora b recruitment to mitotic microtubules. Dev Cell. 2016;36:63–78.Article

Krupina K，Kleiss C，Metzger T，Fournane S，Schmucker S，Hofmann K等。泛素受体蛋白UBASH3B驱动aurora b募集到有丝分裂微管中。开发单元。2016年；36:63–78.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Bertelsen V, Breen K, Sandvig K, Stang E, Madshus IH. The Cbl-interacting protein TULA inhibits dynamin-dependent endocytosis. Exp Cell Res. 2007;313:1696–709.Article

。Cbl相互作用蛋白TULA抑制动力蛋白依赖性内吞作用。Exp Cell Res.2007；313:1696–709.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Voisinne G, Kersse K, Chaoui K, Lu L, Chaix J, Zhang L, et al. Quantitative interactomics in primary T cells unveils TCR signal diversification extent and dynamics. Nat Immunol. 2019;20:1530–41.Article

Voisinne G，Kersse K，Chaoui K，Lu L，Chaix J，Zhang L等。原代T细胞中的定量相互作用组学揭示了TCR信号多样化的程度和动态。Nat免疫。2019年；20： 1530-41.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Voisinne G, García-Blesa A, Chaoui K, Fiore F, Bergot E, Girard L, et al. Co-recruitment analysis of the CBL and CBLB signalosomes in primary T cells identifies CD5 as a key regulator of TCR-induced ubiquitylation. Mol Syst Biol. 2016;12:876.Article

Voisinne G，García-Blesa a，Chaoui K，Fiore F，Bergot E，Girard L等。原代T细胞中CBL和CBLB信号体的共募集分析将CD5鉴定为TCR诱导的泛素化的关键调节剂。摩尔系统生物学。2016年；12： 第876条

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Ge Y, Paisie TK, Chen S, Concannon P. UBASH3A regulates the synthesis and dynamics of TCR-CD3 complexes. J Immunol. 2019;203:2827–36.Article

Ge Y，Paisie TK，Chen S，Concannon P.UBASH3A调节TCR-CD3复合物的合成和动力学。免疫杂志。2019年；203:2827–36.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Tsai Y-L, Arias-Badia M, Kadlecek TA, Lwin YM, Srinath A, Shah NH, et al. TCR signaling promotes formation of an STS1-Cbl-b complex with pH-sensitive phosphatase activity that suppresses T cell function in acidic environments. Immunity. 2023;56:2682–98.e9.Article

Tsai Y-L，Arias Badia M，Kadlecek TA，Lwin YM，Srinath A，Shah NH等。TCR信号传导促进STS1-Cbl-b复合物的形成，该复合物具有pH敏感的磷酸酶活性，可抑制酸性环境中的T细胞功能。豁免。2023年；56:2682–98.e9.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Mazumder R, Iyer LM, Vasudevan S, Aravind L. Detection of novel members, structure-function analysis and evolutionary classification of the 2H phosphoesterase superfamily. Nucleic Acids Res. 2002;30:5229–43.Article

Mazumder R，Iyer LM，Vasudevan S，Aravind L.2H磷酸酯酶超家族的新成员检测，结构功能分析和进化分类。核酸研究2002；30:5229–43.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Yin Y, Frank D, Zhou W, Kaur N, French JB, Carpino N. An unexpected 2-histidine phosphoesterase activity of suppressor of T-cell receptor signaling protein 1 contributes to the suppression of cell signaling. J Biol Chem. 2020;295:8514–23.Article

Yin Y，Frank D，Zhou W，Kaur N，French JB，Carpino N.T细胞受体信号蛋白1抑制剂的意外2-组氨酸磷酸酯酶活性有助于抑制细胞信号传导。生物化学杂志。2020年；295:8514–23.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Mikhailik A, Ford B, Keller J, Chen Y, Nassar N, Carpino N. A phosphatase activity of Sts-1 contributes to the suppression of TCR signaling. Mol Cell. 2007;27:486–97.Article

Mikhailik A，Ford B，Keller J，Chen Y，Nassar N，Carpino N.Sts-1的磷酸酶活性有助于抑制TCR信号传导。摩尔细胞。2007年；27:486–97.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Agrawal R, Carpino N, Tsygankov A. TULA proteins regulate activity of the protein tyrosine kinase Syk. J Cell Biochem. 2008;104:953–64.Article

Agrawal R，Carpino N，Tsygankov A.TULA蛋白调节蛋白酪氨酸激酶Syk的活性。J细胞生物化学。2008年；104:953–64.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Raguz J, Wagner S, Dikic I, Hoeller D. Suppressor of T-cell receptor signalling 1 and 2 differentially regulate endocytosis and signalling of receptor tyrosine kinases. FEBS Lett. 2007;581:4767–72.Article

。FEBS Lett公司。2007年；581:4767–72.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Zhou W, Yin Y, Weinheimer AS, Kaur N, Carpino N, French JB. Structural and functional characterization of the histidine phosphatase domains of human Sts-1 and Sts-2. Biochemistry. 2017;56:4637–45.Article

周W，尹Y，Weinheimer AS，Kaur N，Carpino N，French JB。人Sts-1和Sts-2组氨酸磷酸酶结构域的结构和功能表征。生物化学。2017年；56:4637–45.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

San Luis B, Sondgeroth B, Nassar N, Carpino N. Sts-2 is a phosphatase that negatively regulates zeta-associated protein (ZAP)-70 and T cell receptor signaling pathways. J Biol Chem. 2011;286:15943–54.Article

圣路易斯B，Sondgeroth B，Nassar N，Carpino N.Sts-2是一种磷酸酶，可负调节zeta相关蛋白（ZAP）-70和T细胞受体信号通路。生物化学杂志。2011年；286:15943–54.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Chen X, Ren L, Kim S, Carpino N, Daniel JL, Kunapuli SP, et al. Determination of the substrate specificity of protein-tyrosine phosphatase TULA-2 and identification of Syk as a TULA-2 substrate. J Biol Chem. 2010;285:31268–76.Article

Chen X，Ren L，Kim S，Carpino N，Daniel JL，Kunapuli SP等。蛋白酪氨酸磷酸酶TULA-2底物特异性的测定和Syk作为TULA-2底物的鉴定。生物化学杂志。2010年；285:31268–76.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Thomas DH, Getz TM, Newman TN, Dangelmaier CA, Carpino N, Kunapuli SP, et al. A novel histidine tyrosine phosphatase, TULA-2, associates with Syk and negatively regulates GPVI signaling in platelets. Blood. 2010;116:2570–8.Article

Thomas DH，Getz TM，Newman TN，Dangelmaier CA，Carpino N，Kunapuli SP等。一种新型组氨酸酪氨酸磷酸酶TULA-2与Syk结合并负调节血小板中的GPVI信号传导。血。2010年；116:2570–8.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Chen Y, Jakoncic J, Parker KA, Carpino N, Nassar N. Structures of the phosphorylated and VO(3)-bound 2H-phosphatase domain of Sts-2. Biochemistry. 2009;48:8129–35.Article

Chen Y，Jakoncic J，Parker KA，Carpino N，Nassar N.Sts-2磷酸化和VO（3）结合的2H磷酸酶结构域的结构。生物化学。2009年；48:8129–35.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Kleinman H, Ford B, Keller J, Carpino N, Nassar N. Crystallization and initial crystal characterization of the C-terminal phosphoglycerate mutase homology domain of Sts-1. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2006;62:218–20.Article

Kleinman H，Ford B，Keller J，Carpino N，Nassar N.Sts-1 C端磷酸甘油酸突变酶同源结构域的结晶和初始晶体表征。晶体学报F节结构生物晶体公社。2006年；62:218-20.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Yang M, Chen T, Li X, Yu Z, Tang S, Wang C, et al. K33-linked polyubiquitination of Zap70 by Nrdp1 controls CD8(+) T cell activation. Nat Immunol. 2015;16:1253–62.Article

Yang M，Chen T，Li X，Yu Z，Tang S，Wang C等。Nrdp1对Zap70的K33连接多泛素化控制CD8（+）T细胞活化。Nat免疫。2015年；16： 1253-62.条

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Hu H, Wang H, Xiao Y, Jin J, Chang J-H, Zou Q, et al. Otud7b facilitates T cell activation and inflammatory responses by regulating Zap70 ubiquitination. J Exp Med. 2016;213:399–414.Article

Hu H，Wang H，Xiao Y，Jin J，Chang J-H，Zou Q等。Otud7b通过调节Zap70泛素化促进T细胞活化和炎症反应。J Exp Med。2016；213:399–414.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Alcover A, Alarcón B. Internalization and intracellular fate of TCR-CD3 complexes. Crit Rev Immunol. 2000;20:325–46.Article

Alcover A，Alarcón B.TCR-CD3复合物的内在化和细胞内命运。Crit Rev免疫。2000年；20： 325-46.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Geisler C. TCR trafficking in resting and stimulated T cells. Crit Rev Immunol. 2004;24:67–86.Article

Geisler C.TCR在静息和刺激的T细胞中的运输。Crit Rev免疫。；

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Liu H, Rhodes M, Wiest DL, Vignali DA. On the dynamics of TCR:CD3 complex cell surface expression and downmodulation. Immunity. 2000;13:665–75.Article

Liu H，Rhodes M，Wiest DL，Vignali DA。关于TCR的动力学：CD3复合细胞表面表达和下调。豁免。2000年；13： 665-75.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Thien CBF, Langdon WY. c-Cbl and Cbl-b ubiquitin ligases: substrate diversity and the negative regulation of signalling responses. Biochem J. 2005;391:153–66.Article

Thien CBF，Langdon WY.c-Cbl和Cbl-b泛素连接酶：底物多样性和信号反应的负调控。生物化学J.2005；391:153–66.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Lutz-Nicoladoni C, Wolf D, Sopper S. Modulation of immune cell functions by the E3 ligase Cbl-b. Front Oncol. 2015;5:58.Article

Lutz Nicoladoni C，Wolf D，Sopper S.通过E3连接酶Cbl-b调节免疫细胞功能。Front Oncol。2015年；5： 58、条款

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Wang HY, Altman Y, Fang D, Elly C, Dai Y, Shao Y, et al. Cbl promotes ubiquitination of the T cell receptor zeta through an adaptor function of Zap-70. J Biol Chem. 2001;276:26004–11.Article

Wang HY，Altman Y，Fang D，Elly C，Dai Y，Shao Y等。Cbl通过Zap-70的衔接子功能促进T细胞受体zeta的泛素化。生物化学杂志。2001年；276:26004–11.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Rao N, Miyake S, Reddi AL, Douillard P, Ghosh AK, Dodge IL, et al. Negative regulation of Lck by Cbl ubiquitin ligase. Proc Natl Acad Sci. 2002;99:3794–9.Article

。美国国家科学院院刊。2002年；99:3794–9.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Balagopalan L, Barr VA, Sommers CL, Barda-Saad M, Goyal A, Isakowitz MS, et al. c-Cbl-mediated regulation of LAT-nucleated signaling complexes. Mol Cell Biol. 2007;27:8622–36.Article

。摩尔细胞生物学。2007年；27:8622–36.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Bachmaier K, Krawczyk C, Kozieradzki I, Kong YY, Sasaki T, Oliveira-dos-Santos A, et al. Negative regulation of lymphocyte activation and autoimmunity by the molecular adaptor Cbl-b. Nature. 2000;403:211–6.Article

Bachmaier K，Krawczyk C，Kozieradzki I，Kong YY，Sasaki T，Oliveira dos Santos A等。分子衔接子Cbl-b对淋巴细胞活化和自身免疫的负调控。Nature。2000年；403:211–6.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Chiang YJ, Kole HK, Brown K, Naramura M, Fukuhara S, Hu RJ, et al. Cbl-b regulates the CD28 dependence of T-cell activation. Nature. 2000;403:216–20.Article

Chiang YJ，Kole HK，Brown K，Naramura M，Fukuhara S，Hu RJ等。Cbl-b调节T细胞活化的CD28依赖性。自然。2000年；403:216–20.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Shifrut E, Carnevale J, Tobin V, Roth TL, Woo JM, Bui CT, et al. Genome-wide CRISPR screens in primary human T cells reveal key regulators of immune function. Cell. 2018;175:1958–71.e15.Article

Shifrat E，Carnevale J，Tobin V，Roth TL，Woo JM，Bui CT等。原代人T细胞中的全基因组CRISPR筛选揭示了免疫功能的关键调节因子。细胞。2018年；175:1958–71.e15.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Hayden MS, Ghosh S. NF-κB, the first quarter-century: remarkable progress and outstanding questions. Genes Dev. 2012;26:203–34.Article

Hayden MS，Ghosh S.NF-κB，第一个四分之一世纪：显着的进步和悬而未决的问题。Genes Dev.2012；26:203–34.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Pahl HL. Activators and target genes of Rel/NF-kappaB transcription factors. Oncogene. 1999;18:6853–66.Article

帕尔HL。Rel/NF-κB转录因子的激活剂和靶基因。致癌基因。1999年；18： 6853-66.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Chen ZJ. Ubiquitination in signaling to and activation of IKK. Immunol Rev. 2012;246:95–106.Article

陈志杰。IKK信号传导和激活中的泛素化。；246:95–106.文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Wertz IE, Dixit VM. Signaling to NF-kappaB: regulation by ubiquitination. Cold Spring Harb Perspect Biol. 2010;2:a003350.Article

Wertz IE，Dixit VM。向NF-κB发出信号：通过泛素化调节。冷泉Harb Perspect Biol。2010年；2： a003350。条款

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Spolski R, Li P, Leonard WJ. Biology and regulation of IL-2: from molecular mechanisms to human therapy. Nat Rev Immunol. 2018;18:648–59.Article

斯波尔斯基R，李P，伦纳德WJ。IL-2的生物学和调控：从分子机制到人类治疗。Nat Rev免疫。2018年；18： 648-59.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Hope JL, Otero DC, Bae E-A, Stairiker CJ, Palete AB, Faso HA, et al. PSGL-1 attenuates early TCR signaling to suppress CD8+ T cell progenitor differentiation and elicit terminal CD8+ T cell exhaustion. Cell Rep. 2023;42:112436.Article

Hope JL，Otero DC，Bae E-A，Stairiker CJ，Palette AB，Fasofa HA等。PSGL-1减弱早期TCR信号传导以抑制CD8+T细胞祖细胞分化并引发末端CD8+T细胞耗竭。细胞代表2023；42:112436.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Newman TN, Liverani E, Ivanova E, Russo GL, Carpino N, Ganea D, et al. Members of the novel UBASH3/STS/TULA family of cellular regulators suppress T-cell-driven inflammatory responses in vivo. Immunol Cell Biol. 2014;92:837–50.Article

Newman TN，Liverani E，Ivanova E，Russo GL，Carpino N，Ganea D等。新型UBASH3/STS/TULA细胞调节剂家族的成员在体内抑制T细胞驱动的炎症反应。免疫细胞生物学。2014年；92:837–50.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Okabe N, Ohmura K, Katayama M, Akizuki S, Carpino N, Murakami K, et al. Suppressor of TCR signaling-2 (STS-2) suppresses arthritis development in mice. Mod Rheumatol. 2018;28:626–36.Article

Okabe N，Ohmura K，Katayama M，Akizuki S，Carpino N，Murakami K等。TCR信号传导抑制因子-2（STS-2）抑制小鼠关节炎的发展。Mod风湿病。2018年；28:626–36.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Chen Y-G, Ciecko AE, Khaja S, Grzybowski M, Geurts AM, Lieberman SM. UBASH3A deficiency accelerates type 1 diabetes development and enhances salivary gland inflammation in NOD mice. Sci Rep. 2020;10:12019.Article

Chen Y-G，Ciecko AE，Khaja S，Grzybowski M，Geurts AM，Lieberman SM。UBASH3A缺乏会加速1型糖尿病的发展并增强NOD小鼠的唾液腺炎症。Sci Rep.2020；10： 第12019条

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Mordes JP, Cort L, Liu Z, Eberwine R, Blankenhorn EP, Pierce BG. T cell receptor genotype and Ubash3a determine susceptibility to rat autoimmune diabetes. Genes. 2021;12. https://doi.org/10.3390/genes12060852.International Multiple Sclerosis Genetics Consortium. Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility.

Mordes JP，Cort L，Liu Z，Eberwine R，Blankenhorn EP，Pierce BG。T细胞受体基因型和Ubash3a决定了对大鼠自身免疫性糖尿病的易感性。基因。2021年；12https://doi.org/10.3390/genes12060852.International多发性硬化症遗传学联盟。。

Science. 2019;365:eaav7188.Article .

科学。2019年；365:EAAV7188.文章。

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Gao J, Zhu C, Zhang Y, Sheng Y, Yang F, Wang W, et al. Association study and fine-mapping major histocompatibility complex analysis of Pemphigus Vulgaris in a Han Chinese population. J Investig Dermatol. 2018;138:2307–14.Article

高J，朱C，张Y，盛Y，杨F，王W，等。汉族人群寻常型天疱疮的关联研究和精细定位主要组织相容性复合体分析。J调查皮肤病。2018年；138:2307–14.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Fei Y, Webb R, Cobb BL, Direskeneli H, Saruhan-Direskeneli G, Sawalha AH. Identification of novel genetic susceptibility loci for Behçet’s disease using a genome-wide association study. Arthritis Res Ther. 2009;11:R66.Article

费Y，韦伯R，科布BL，迪雷斯肯内利H，萨鲁汉·迪雷斯肯内利G，萨瓦哈AH。使用全基因组关联研究鉴定Behçet病的新型遗传易感基因座。关节炎。2009年；11： R66条款

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Shahriyari E, Bonyadi M, Jabbarpoor Bonyadi MH, Soheilian M, Yaseri M, Ebrahimiadib N. Ubiquitin associated and SH3 domain-containing B (UBASH3B) gene association with Behcet’s disease in Iranian population. Curr Eye Res. 2019;44:200–5.Article

。Curr Eye Res.2019；44:200–5.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Concannon P, Onengut-Gumuscu S, Todd JA, Smyth DJ, Pociot F, Bergholdt R, et al. A human type 1 diabetes susceptibility locus maps to chromosome 21q22.3. Diabetes. 2008;57:2858–61.Article

Concannon P，Onengut Gumuscu S，Todd JA，Smyth DJ，Pociot F，Bergholdt R等。人类1型糖尿病易感基因座定位于染色体21q22.3。糖尿病。2008年；57:2858–61.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Grant SFA, Qu H-Q, Bradfield JP, Marchand L, Kim CE, Glessner JT, et al. Follow-up analysis of genome-wide association data identifies novel loci for type 1 diabetes. Diabetes. 2009;58:290–5.Article

。糖尿病。2009年；58:290–5.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Barrett JC, Clayton DG, Concannon P, Akolkar B, Cooper JD, Erlich HA, et al. Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes. Nat Genet. 2009;41:703–7.Article

Barrett JC，Clayton DG，Concannon P，Akolkar B，Cooper JD，Erlich HA等。全基因组关联研究和荟萃分析发现，超过40个基因座影响1型糖尿病的风险。纳特·吉内特。2009年；41:703–7.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Jin Y, Birlea SA, Fain PR, Gowan K, Riccardi SL, Holland PJ, et al. Variant of TYR and autoimmunity susceptibility loci in generalized vitiligo. N Engl J Med. 2010;362:1686–97.Article

Jin Y，Birlea SA，Fain PR，Gowan K，Riccardi SL，Holland PJ等。全身性白癜风中TYR和自身免疫易感基因座的变异。英国医学杂志2010；362:1686–97.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Trynka G, Hunt KA, Bockett NA, Romanos J, Mistry V, Szperl A, et al. Dense genotyping identifies and localizes multiple common and rare variant association signals in celiac disease. Nat Genet. 2011;43:1193–201.Article

Trynka G，Hunt KA，Bockett NA，Romanos J，Mistry V，Szperl A等。密集基因分型可识别和定位乳糜泻中多种常见和罕见的变异关联信号。纳特·吉内特。2011年；43:1193-201.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Okada Y, Wu D, Trynka G, Raj T, Terao C, Ikari K, et al. Genetics of rheumatoid arthritis contributes to biology and drug discovery. Nature. 2014;506:376–81.Article

冈田Y，Wu D，Trynka G，Raj T，Terao C，Ikari K等。类风湿性关节炎的遗传学有助于生物学和药物发现。自然。2014年；506:376–81.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Kim K, Bang S-Y, Lee H-S, Cho S-K, Choi C-B, Sung Y-K, et al. High-density genotyping of immune loci in Koreans and Europeans identifies eight new rheumatoid arthritis risk loci. Ann Rheum Dis. 2015;74:e13.Article

Kim K，Bang S-Y，Lee H-S，Cho S-K，Choi C-B，Sung Y-K等。韩国人和欧洲人免疫基因座的高密度基因分型确定了八个新的类风湿性关节炎风险基因座。安·瑞姆·迪斯。2015年；74:e13.文章

PubMed

PubMed

Google Scholar

谷歌学者

Jin Y, Andersen G, Yorgov D, Ferrara TM, Ben S, Brownson KM, et al. Genome-wide association studies of autoimmune vitiligo identify 23 new risk loci and highlight key pathways and regulatory variants. Nat Genet. 2016;48:1418–24.Article

Jin Y，Andersen G，Yorgov D，Ferrara TM，Ben S，Brownson KM等。自身免疫性白癜风的全基因组关联研究确定了23个新的风险位点，并突出了关键途径和调控变异。纳特·吉内特。2016年；48:1418–24.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Ji S-G, Juran BD, Mucha S, Folseraas T, Jostins L, Melum E, et al. Genome-wide association study of primary sclerosing cholangitis identifies new risk loci and quantifies the genetic relationship with inflammatory bowel disease. Nat Genet. 2017;49:269–73.Article

Ji S-G，Juran BD，Mucha S，Folseraas T，Jostins L，Melum E等。原发性硬化性胆管炎的全基因组关联研究确定了新的风险位点，并量化了与炎症性肠病的遗传关系。纳特·吉内特。2017年；49:269–73.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Sakaue S, Kanai M, Tanigawa Y, Karjalainen J, Kurki M, Koshiba S, et al. A cross-population atlas of genetic associations for 220 human phenotypes. Nat Genet. 2021;53:1415–24.Article

Sakaue S，Kanai M，Tanigawa Y，Karjalainen J，Kurki M，Koshiba S等。220种人类表型的遗传关联跨群体图谱。纳特·吉内特。2021年；53:1415–24.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Eriksson D, Røyrvik EC, Aranda-Guillén M, Berger AH, Landegren N, Artaza H, et al. GWAS for autoimmune Addison’s disease identifies multiple risk loci and highlights AIRE in disease susceptibility. Nat Commun. 2021;12:959.Article

Eriksson D，Røyrvik EC，Aranda Guillén M，Berger AH，Landegren n，Artaza H等。GWAS针对自身免疫性艾迪生病确定了多个风险位点，并突出了AIRE在疾病易感性中的作用。纳特公社。2021年；12： 第959条

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Han Y, Jia Q, Jahani PS, Hurrell BP, Pan C, Huang P, et al. Genome-wide analysis highlights contribution of immune system pathways to the genetic architecture of asthma. Nat Commun. 2020;11:1776.Article

Han Y，Jia Q，Jahani PS，Hurrell BP，Pan C，Huang P等。全基因组分析强调了免疫系统途径对哮喘遗传结构的贡献。纳特公社。2020年；11： 1776条

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Zhernakova A, Stahl EA, Trynka G, Raychaudhuri S, Festen EA, Franke L, et al. Meta-analysis of genome-wide association studies in celiac disease and rheumatoid arthritis identifies fourteen non-HLA shared loci. PLoS Genet. 2011;7:e1002004.Article

Zhernakova A，Stahl EA，Trynka G，Raychaudhuri S，Festen EA，Franke L等。乳糜泻和类风湿性关节炎全基因组关联研究的荟萃分析确定了14个非HLA共享基因座。PLoS Genet。2011年；7： e1002004。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Márquez A, Kerick M, Zhernakova A, Gutierrez-Achury J, Chen W-M, Onengut-Gumuscu S, et al. Meta-analysis of Immunochip data of four autoimmune diseases reveals novel single-disease and cross-phenotype associations. Genome Med. 2018;10:97.Article

Márquez A，Kerick M，Zhernakova A，Gutierrez-Achury J，Chen W-M，Onegut-Gumuscu S等。对四种自身免疫性疾病的免疫芯片数据的荟萃分析揭示了新的单一疾病和交叉表型关联。基因组医学2018；10： 97、条款

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Ge Y, Concannon P. Molecular-genetic characterization of common, noncoding UBASH3A variants associated with type 1 diabetes. Eur J Hum Genet. 2018;26:1060–4.Article

Ge Y，Concannon P.与1型糖尿病相关的常见非编码UBASH3A变体的分子遗传学表征。Eur J Hum Genet。2018年；26:1060–4.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Robertson CC, Inshaw JRJ, Onengut-Gumuscu S, Chen W-M, Santa Cruz DF, Yang H, et al. Fine-mapping, trans-ancestral and genomic analyses identify causal variants, cells, genes and drug targets for type 1 diabetes. Nat Genet. 2021;53:962–71.Article

Robertson CC，Inshaw JRJ，Onegut Gumuscu S，Chen W-M，Santa Cruz DF，Yang H等人。精细定位，跨祖先和基因组分析确定了1型糖尿病的因果变异，细胞，基因和药物靶标。纳特·吉内特。2021年；53:962–71.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Newman JRB, Conesa A, Mika M, New FN, Onengut-Gumuscu S, Atkinson MA, et al. Disease-specific biases in alternative splicing and tissue-specific dysregulation revealed by multitissue profiling of lymphocyte gene expression in type 1 diabetes. Genome Res. 2017;27:1807–15.Article

Newman JRB，Conesa A，Mika M，New FN，Onegut Gumuscu S，Atkinson MA等。1型糖尿病淋巴细胞基因表达的多组织分析揭示了选择性剪接和组织特异性失调的疾病特异性偏倚。基因组研究2017；27:1807–15.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Kaye WA, Adri MN, Soeldner JS, Rabinowe SL, Kaldany A, Kahn CR, et al. Acquired defect in interleukin-2 production in patients with type I diabetes mellitus. N Engl J Med. 1986;315:920–4.Article

Kaye WA，Adri MN，Soeldner JS，Rabinowe SL，Kaldany A，Kahn CR等。I型糖尿病患者白细胞介素-2产生缺陷。英格兰医学杂志1986；315:920–4.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Roncarolo MG, Zoppo M, Bacchetta R, Gabiano C, Sacchetti C, Cerutti F, et al. Interleukin-2 production and interleukin-2 receptor expression in children with newly diagnosed diabetes. Clin Immunol Immunopathol. 1988;49:53–62.Article

。临床免疫免疫病理学。1988年；49:53–62.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Alcocer-Varela J, Alarcón-Segovia D. Decreased production of and response to interleukin-2 by cultured lymphocytes from patients with systemic lupus erythematosus. J Clin Investig. 1982;69:1388–92.Article

Alcocer Varela J，Alarcón-Segovia D.降低了系统性红斑狼疮患者培养淋巴细胞产生白细胞介素-2的能力和对白细胞介素-2的反应。J临床研究。1982年；69:1388–92.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Linker-Israeli M, Bakke AC, Kitridou RC, Gendler S, Gillis S, Horwitz DA. Defective production of interleukin 1 and interleukin 2 in patients with systemic lupus erythematosus (SLE). J Immunol. 1983;130:2651–5.Article

Linker Israel M，Bakke AC，Kitridou RC，Gendler S，Gillis S，Horwitz DA。系统性红斑狼疮（SLE）患者白细胞介素1和白细胞介素2产生缺陷。免疫杂志。1983年；130:2651–5.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Combe B, Pope RM, Fischbach M, Darnell B, Baron S, Talal N. Interleukin-2 in rheumatoid arthritis: production of and response to interleukin-2 in rheumatoid synovial fluid, synovial tissue and peripheral blood. Clin Exp Immunol. 1985;59:520–8.CAS

Combe B，Pope RM，Fischbach M，Darnell B，Baron S，Talal N.类风湿性关节炎中的白细胞介素-2：类风湿性滑液，滑膜组织和外周血中白细胞介素-2的产生和反应。临床实验免疫。1985年；59:520–8.CAS

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Yamagata K, Nakayamada S, Zhang T, Nguyen AP, Ohkubo N, Iwata S, et al. IL-6 production through repression of UBASH3A gene via epigenetic dysregulation of super-enhancer in CD4(+) T cells in rheumatoid arthritis. Inflamm Regen. 2022;42:46.Article

Yamagata K，Nakayamada S，Zhang T，Nguyen AP，Ohkubo N，Iwata S等。通过类风湿性关节炎CD4（+）T细胞中超增强子的表观遗传失调抑制UBASH3A基因产生IL-6。炎症再生。2022年；42:46.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Zhou W, Yin Y, Smith E, Chou J, Shumate J, Scampavia L, et al. Discovery and characterization of two classes of selective inhibitors of the suppressor of the TCR signaling family of proteins. ACS Infect Dis. 2019;5:250–9.Article

Zhou W，Yin Y，Smith E，Chou J，Shumate J，Scampavia L等。TCR信号传导蛋白家族抑制剂的两类选择性抑制剂的发现和表征。ACS感染Dis。2019年；5： 250–9.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Li N, Wang Y, Wang A, Zhang J, Jia C, Yu C, et al. STS1 and STS2 phosphatase inhibitor baicalein enhances the expansion of hematopoietic and progenitor stem cells and alleviates 5-fluorouracil-induced myelosuppression. Int J Mol Sci. 2023;24:2987.Article

Li N，Wang Y，Wang A，Zhang J，Jia C，Yu C等。STS1和STS2磷酸酶抑制剂黄芩素增强造血干细胞和祖细胞的扩增，减轻5-氟尿嘧啶诱导的骨髓抑制。。2023年；24:2987.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

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Download referencesAcknowledgementsThis work was supported by Juvenile Diabetes Research Foundation (grant numbers 3-APF-2016-177-A-N, 1-FAC-2019-802-A-N) to YG; a Talent Award from Taizhou City, China to YG; and the National Institute of Diabetes and Digestive and Kidney Diseases (grant number DK106718) to PC.Author informationAuthors and AffiliationsInternational Center for Genetic Engineering and Biotechnology, China Regional Research Center, Taizhou, Jiangsu Province, ChinaHua Wang & Yan GeGenetics Institute, University of Florida, Gainesville, FL, USAPatrick ConcannonDepartment of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL, USAPatrick ConcannonAuthorsHua WangView author publicationsYou can also search for this author in.

下载参考文献致谢这项工作得到了青少年糖尿病研究基金会（授权号3-APF-2016-177-A-N，1-FAC-2019-802-A-N）对YG的支持；中国台州市向YG颁发人才奖；以及国家糖尿病、消化和肾脏疾病研究所（授权号DK106718）授予PC。作者信息作者和附属机构中国区域研究中心国际基因工程与生物技术中心，江苏省泰州，中国华旺和Yan GeGenetics Institute，佛罗里达大学，佛罗里达州盖恩斯维尔，美国佛罗里达大学Patrick ConcannonDepartment of Pathology，Immunology and Laboratory Medicine，佛罗里达州盖恩斯维尔，美国Patrick ConcannonAuthorsHua WangView作者出版物您也可以在中搜索这位作者。

PubMed Google ScholarPatrick ConcannonView author publicationsYou can also search for this author in

PubMed Google ScholarPatrick ConcannonView作者出版物您也可以在

PubMed Google ScholarYan GeView author publicationsYou can also search for this author in

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PubMed Google ScholarContributionsConceptualization, Writing–original draft, and Writing–review & editing: HW, PC, and YG.Corresponding authorCorrespondence to

PubMed谷歌学术贡献概念化，写作-原稿，写作-评论和编辑：HW，PC和YG。对应作者对应

Yan Ge.Ethics declarations

严格.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。

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Additional informationPublisher的注释Springer Nature在已发布的地图和机构隶属关系中的管辖权主张方面保持中立。权利和许可Pringer Nature或其许可人（例如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，对本文拥有独家权利；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Wang，H.，Concannon，P。

& Ge, Y. Roles of TULA-family proteins in T cells and autoimmune diseases..

&Ge，Y.TULA家族蛋白在T细胞和自身免疫性疾病中的作用。。

Genes Immun (2024). https://doi.org/10.1038/s41435-024-00300-8Download citationReceived: 09 July 2024Revised: 28 September 2024Accepted: 01 October 2024Published: 18 November 2024DOI: https://doi.org/10.1038/s41435-024-00300-8Share 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.

基因免疫（2024）。https://doi.org/10.1038/s41435-024-00300-8Download引文收到日期：2024年7月9日修订日期：2024年9月28日接受日期：2024年10月1日发布日期：2024年11月18日OI：https://doi.org/10.1038/s41435-024-00300-8Share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。

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AutoimmunityDisease geneticsGenetic predisposition to diseaseLymphocyte activationNF-kappaB

自身免疫性疾病遗传易感性疾病淋巴细胞活化NF-κB