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T-cell regulator RNF125/TRAC-1 belongs to a novel family of ubiquitin ligases with zinc fingers and a ubiquitin-binding domain.

The recently identified RNF125 [RING (really interesting new gene) finger protein 125], or TRAC-1 (T-cell RING protein in activation 1), is unique among ubiquitin ligases in being a positive regulator of T-cell activation. In addition, TRAC-1 has been shown to down-modulate HIV replication and to inhibit pathogen-induced cytokine production. However, apart from the presence of an N-terminal C3HC4 (Cys(3)-His-Cys(4)) RING domain, the TRAC-1 protein remains uncharacterized. In the present paper, we report novel interactions and modifications for TRAC-1, and elucidate its domain organization. Specifically, we determine that TRAC-1 associates with membranes and is excluded from the nucleus through myristoylation. Our data are further consistent with a crucial role for the C-terminus in TRAC-1 function. In this region, novel domains were recognized through the identification of three closely related proteins: RNF114, RNF138 and RNF166. TRAC-1 and its relatives were found to contain, apart from the RING domain, a C2HC (Cys(2)-His-Cys)- and two C2H2 (Cys(2)-His(2))-type zinc fingers, as well as a UIM (ubiquitin-interacting motif). The UIM of TRAC-1 binds Lys(48)-linked polyubiquitin chains and is, together with the RING domain, required for auto-ubiquitination. As a consequence of auto-ubiquitination, the half-life of TRAC-1 is shorter than 30 min. The identification of these novel modifications, interactions, domains and relatives significantly widens the contexts for investigating TRAC-1 activity and regulation.

Pubmed ID: 17990982

Authors

  • Giannini AL
  • Gao Y
  • Bijlmakers MJ

Journal

The Biochemical journal

Publication Data

February 15, 2008

Associated Grants

  • Agency: Wellcome Trust, Id: 078170
  • Agency: Wellcome Trust, Id:

Mesh Terms

  • Binding Sites
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Humans
  • Jurkat Cells
  • Lymphocyte Activation
  • Nuclear Proteins
  • Nuclear Receptor Co-Repressor 1
  • Repressor Proteins
  • T-Lymphocytes
  • Ubiquitin
  • Zinc Fingers