A novel E3 ubiquitin ligase TRAC-1 positively regulates T cell activation
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.
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
2005 |
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| Erschienen: |
2005 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:174 |
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| Enthalten in: |
Journal of immunology (Baltimore, Md. : 1950) - 174(2005), 9 vom: 01. Mai, Seite 5288-97 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhao, Haoran [VerfasserIn] |
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| Anmerkungen: |
Date Completed 21.06.2005 Date Revised 16.05.2019 published: Print Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM154924768 |
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| 100 | 1 | |a Zhao, Haoran |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A novel E3 ubiquitin ligase TRAC-1 positively regulates T cell activation |
| 264 | 1 | |c 2005 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ohne Hilfsmittel zu benutzen |b n |2 rdamedia | ||
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| 500 | |a Date Completed 21.06.2005 | ||
| 500 | |a Date Revised 16.05.2019 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 7 | |a Ubiquitin-Protein Ligases |2 NLM | |
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| 700 | 1 | |a Li, Connie C |e verfasserin |4 aut | |
| 700 | 1 | |a Pardo, Jorge |e verfasserin |4 aut | |
| 700 | 1 | |a Chu, Peter C |e verfasserin |4 aut | |
| 700 | 1 | |a Liao, Charlene X |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Jianing |e verfasserin |4 aut | |
| 700 | 1 | |a Dong, John G |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Xiulan |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Qi |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Betty |e verfasserin |4 aut | |
| 700 | 1 | |a Bennett, Mark K |e verfasserin |4 aut | |
| 700 | 1 | |a Molineaux, Susan M |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Henry |e verfasserin |4 aut | |
| 700 | 1 | |a Daniel-Issakani, Sarkiz |e verfasserin |4 aut | |
| 700 | 1 | |a Payan, Donald G |e verfasserin |4 aut | |
| 700 | 1 | |a Masuda, Esteban S |e verfasserin |4 aut | |
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