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)

Abstract

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.

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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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