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Related Concept Videos

T Cell Activation and Clonal Selection01:22

T Cell Activation and Clonal Selection

T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...
Diversity of Antigen Receptors01:28

Diversity of Antigen Receptors

Antigen receptors are essential components of the immune system crucial in defending the body against foreign invaders. These receptors are present on the surface of B and T cells, enabling them to recognize antigens and mount an appropriate immune response.
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...
Regulated Protein Degradation02:58

Regulated Protein Degradation

It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Anaphase Promoting Complex00:50

Anaphase Promoting Complex

The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.

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Related Experiment Video

Updated: Jun 16, 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

Tonic ubiquitylation controls T-cell receptor:CD3 complex expression during T-cell development.

Haopeng Wang1, Jeff Holst, Seng-Ryong Woo

  • 1Department of Immunology, St Jude Children's Research Hospital, Memphis, TN, USA.

The EMBO Journal
|February 13, 2010
PubMed
Summary

Tonic ubiquitylation of the T-cell receptor (TCR):CD3 complex in immature thymocytes precisely regulates TCR expression. This process is crucial for T-cell development and preventing signaling errors.

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Last Updated: Jun 16, 2026

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

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Published on: March 22, 2012

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Published on: April 25, 2018

In Vitro Ubiquitination and Deubiquitination Assays of Nucleosomal Histones
11:36

In Vitro Ubiquitination and Deubiquitination Assays of Nucleosomal Histones

Published on: July 25, 2019

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • T-cell receptor (TCR):CD3 complex expression is critical for T-cell development.
  • The precise mechanisms and physiological roles of TCR:CD3 regulation during T-cell development remain largely unknown.

Purpose of the Study:

  • To elucidate the mechanism and physiological significance of TCR:CD3 complex regulation during T-cell development.
  • To investigate the role of ubiquitylation in controlling surface TCR:CD3 expression levels.

Main Methods:

  • Analysis of TCR:CD3 ubiquitylation status in different T-cell populations (DP, SP, splenic T cells).
  • Mutation of CD3 cytoplasmic tail lysines to block ubiquitylation.
  • Expression of CD3zeta-monoubiquitin fusion molecules.
  • Assessment of TCR levels, immunological synapse formation, and Erk phosphorylation.

Main Results:

  • TCR:CD3 complex is constitutively ubiquitylated in immature double positive (DP) thymocytes, but not in mature T cells.
  • This ubiquitylation, mediated by CD3ε, Lck, c-Cbl, and SLAP, leads to TCR:CD3 degradation.
  • Blocking ubiquitylation increases DP thymocyte TCR levels, while mimicking ubiquitylation decreases them.
  • Modulation of CD3 ubiquitylation impacts immunological synapse formation, Erk phosphorylation, and T-cell selection thresholds.

Conclusions:

  • Constitutive TCR:CD3 ubiquitylation in DP thymocytes is a key regulatory mechanism for controlling surface receptor expression.
  • This tonic ubiquitylation ensures precise TCR expression levels, maintaining the fidelity of T-cell development and selection processes.