Document Detail


A novel E3 ubiquitin ligase TRAC-1 positively regulates T cell activation.
MedLine Citation:
PMID:  15843525     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Haoran Zhao; Connie C Li; Jorge Pardo; Peter C Chu; Charlene X 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
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  174     ISSN:  0022-1767     ISO Abbreviation:  J. Immunol.     Publication Date:  2005 May 
Date Detail:
Created Date:  2005-04-21     Completed Date:  2005-06-21     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5288-97     Citation Subset:  AIM; IM    
Affiliation:
Rigel Pharmaceuticals, Inc., South San Francisco, CA 94080, USA. hzhao@rigel.com
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Motifs
Amino Acid Sequence
Base Sequence
Catalysis
Cell Cycle Proteins / biosynthesis,  genetics,  isolation & purification,  physiology*
Cell Line
Cell Line, Tumor
DNA-Binding Proteins
Humans
Jurkat Cells
Lymphocyte Activation / genetics,  immunology*
Lymphoid Tissue / cytology,  enzymology,  immunology
Molecular Sequence Data
Nuclear Proteins / biosynthesis,  genetics,  isolation & purification,  physiology*
Nuclear Receptor Co-Repressor 2
Peptide Fragments / genetics,  metabolism
Polyubiquitin / metabolism
Receptors, Antigen, T-Cell / physiology
Repressor Proteins
Saccharomyces cerevisiae Proteins / metabolism
Signal Transduction / genetics,  immunology
T-Lymphocytes / enzymology*,  immunology*,  metabolism
Transcription Factors / metabolism
Ubiquitin-Conjugating Enzymes / metabolism
Ubiquitin-Protein Ligases / biosynthesis,  genetics,  isolation & purification,  physiology*
Up-Regulation / genetics,  immunology*
Chemical
Reg. No./Substance:
0/Cell Cycle Proteins; 0/DNA-Binding Proteins; 0/NCOR2 protein, human; 0/Nuclear Proteins; 0/Nuclear Receptor Co-Repressor 2; 0/Peptide Fragments; 0/Receptors, Antigen, T-Cell; 0/Repressor Proteins; 0/Saccharomyces cerevisiae Proteins; 0/Transcription Factors; 120904-94-1/Polyubiquitin; EC 6.3.2.19/UBC13 protein, S cerevisiae; EC 6.3.2.19/UBE2D3 protein, human; EC 6.3.2.19/UBE2V1 protein, human; EC 6.3.2.19/Ubiquitin-Conjugating Enzymes; EC 6.3.2.19/Ubiquitin-Protein Ligases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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