A novel E3 ubiquitin ligase TRAC-1 positively regulates T cell activation

被引：54

作者：

Zhao, HR ^{[1
]}

Li, CC ^{[1
]}

Pardo, J ^{[1
]}

Chu, PC ^{[1
]}

Liao, CX ^{[1
]}

Huang, JN ^{[1
]}

Dong, JG ^{[1
]}

Zhou, XL ^{[1
]}

Huang, Q ^{[1
]}

Huang, B ^{[1
]}

Bennett, MK ^{[1
]}

Molineaux, SM ^{[1
]}

Lu, H ^{[1
]}

Daniel-Issakani, S ^{[1
]}

Payan, DG ^{[1
]}

Masuda, ES ^{[1
]}

机构：

[1] Rigel Pharmaceut Inc, San Francisco, CA 94080 USA

来源：

JOURNAL OF IMMUNOLOGY | 2005年 / 174卷 / 09期

关键词：

D O I：

10.4049/jimmunol.174.9.5288

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

TRAC-1 (T cell RING (really interesting new gene) protein identified in activation screen) is a novel E3 ubiquitin ligase identified from a retroviral vector-based T cell surface activation marker screen. The C-terminal truncated TRAC-1 specifically inhibited anti-TCR-mediated CD69 up-regulation in Jurkat cells, a human T leukemic cell line. In this study, we show that TRAC-1 is a RING finger ubiquitin E3 ligase with highest expression in lymphoid tissues. Point mutations that disrupt the Zn2+-chelating ability of its amino-terminal RING finger domain abolished TRAC-1's ligase activity and the dominant inhibitory effect of C-terminal truncated TRAC-1 on TCR stimulation. The results of in vitro biochemical studies indicate that TRAC-1 can stimulate the formation of both K48- and K63-linked polyubiquitin chains and therefore could potentially activate both degradative and regulatory ubiquitin-dependent pathways. Antisense oligonucleotides to TRAC-1 specifically reduced TRAC-1 mRNA levels in Jurkat and primary T cells and inhibited their activation in response to TCR cross-linking. Collectively, these results indicate that the E3 ubiquitin ligase TRAC-1 functions as a positive regulator of T cell activation.

引用

页码：5288 / 5297

页数：10

共 52 条

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