Ubiquitination and TRAF signaling

  • Gabriel Pineda
  • Chee-Kwee Ea
  • Zhijian J. Chen
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 597)


Ubiquitin (Ub) is a highly conserved small polypeptide that is ubiquitously expressed in all eukaryotic cells. The best-known function of ubiquitin is to target protein degradation through covalent attachment of this polypeptide on protein substrates. 1, 2, 3This covalent modification, known as ubiquitination, is carried out via a three-step enzymatic cascade. In the first step, Ub is activated by the Ub-activating enzyme (E1) in an ATP-dependent reaction to form an E1-Ub thioester. In the second step, the activated Ub is transferred to a cysteine residue in the active site of a Ub-conjugating enzyme (Ubc or E2) to form an E2-Ub thioester. Finally, in the presence of a Ub-protein ligase (E3), ubiquitin is conjugated to a protein substrate by forming an isopeptide bond between the carboxyl terminus of ubiquitin and the ε-amino group of a lysine residue on the protein target. After Ub is conjugated to a protein substrate, Ub itself can be conjugated by another Ub through one of its seven lysines, typically lysine-48. This process reiterates itself in a highly processive manner to form a polyubiquitin chain, which is then recruited to a large ATP-dependent protease complex called the 26S proteasome. The polyubiquitinated protein substrates are degraded inside the proteasome, whereas the polyubiquitin chains are cleaved to monomeric ubiquitin, which is recycled.


Ubiquitin Ligase Ring Domain Polyubiquitin Chain Mouse Embryonic Fibroblast Cell Tumor Necrosis Factor Receptor Associate Factor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Landes Bioscience and Springer Science+Business Media 2007

Authors and Affiliations

  • Gabriel Pineda
  • Chee-Kwee Ea
  • Zhijian J. Chen
    • 1
  1. 1.Department of Molecular BiologyUniversity of Texas Southwestern Medical CenterDallasUSA

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