Portal de Periódicos da CAPES

A Novel E3 Ubiquitin Ligase TRAC-1 Positively Regulates T Cell Activation

2005; American Association of Immunologists; Volume: 174; Issue: 9 Linguagem: Inglês

10.4049/jimmunol.174.9.5288

1550-6606

H. Zhao, Connie C. Li, Pardo Jorge, Peter C. Chu, Charlene Liao, Jianing Huang, John G. Dong, Xiulan Zhou, Qi Huang, Betty Huang, Mark K. Bennett, Susan M. Molineaux, Henry Lu, Sarkiz Daniel-Issakani, Donald G. Payan, Esteban S. Masuda,

Immune Cell Function and Interaction

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 Zn(2+)-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.