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Updated: Aug 17, 2026

A TIRF Microscopy Technique for Real-time, Simultaneous Imaging of the TCR and its Associated Signaling Proteins
16:10

A TIRF Microscopy Technique for Real-time, Simultaneous Imaging of the TCR and its Associated Signaling Proteins

Published on: March 22, 2012

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

Haoran Zhao1, Connie C Li, Jorge Pardo

  • 1Rigel Pharmaceuticals, Inc., South San Francisco, CA 94080, USA. hzhao@rigel.com

Journal of Immunology (Baltimore, Md. : 1950)
|April 22, 2005
PubMed

Insights

TRAC-1, a novel E3 ubiquitin ligase, positively regulates T cell activation. Inhibiting TRAC-1 in T cells reduces their activation, highlighting its crucial role in immune responses.

Area of Science:

  • Immunology
  • Molecular Biology
  • Biochemistry

Background:

  • TRAC-1 (T cell RING protein identified in activation screen) is a novel E3 ubiquitin ligase.
  • TRAC-1 was identified through a T cell surface activation marker screen.
  • Its role in T cell activation was previously unclear.

Purpose of the Study:

  • To characterize TRAC-1 as an E3 ubiquitin ligase.
  • To investigate TRAC-1's function in T cell activation.
  • To determine the molecular mechanisms underlying TRAC-1's activity.

Main Methods:

  • TRAC-1 expression analysis in lymphoid tissues.
  • Site-directed mutagenesis to disrupt the RING finger domain.
  • In vitro ubiquitination assays to assess polyubiquitin chain formation (K48 and K63).
  • Antisense oligonucleotide treatment in Jurkat and primary T cells.

Main Results:

  • TRAC-1 exhibits highest expression in lymphoid tissues.
  • Disruption of the RING finger domain abolished TRAC-1's ligase activity and inhibitory effects.
  • TRAC-1 promotes both K48- and K63-linked polyubiquitin chain formation.
  • TRAC-1 inhibition reduced T cell activation upon TCR cross-linking.

Conclusions:

  • TRAC-1 functions as a RING finger E3 ubiquitin ligase.
  • TRAC-1 is a positive regulator of T cell activation.
  • TRAC-1's ligase activity is essential for its role in T cell activation.

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