U-box proteins as a new family of ubiquitin ligases

Shigetsugu Hatakeyama, Kei Ichi I. Nakayama

Research output: Contribution to journalReview articlepeer-review

201 Citations (Scopus)


Ubiquitin-protein ligases (E3s) determine the substrate specificity of ubiquitylation and, until recently, had been classified into two families, the HECT and RING-finger families. The U-box is a domain of ∼70 amino acids that is present in proteins from yeast to humans. The prototype U-box protein, yeast Ufd2, was identified as a ubiquitin chain assembly factor (E4) that cooperates with a ubiquitin-activating enzyme (E1), a ubiquitin-conjugating enzyme (E2), and an E3 to catalyze the formation of a ubiquitin chain on artificial substrates. We recently showed that mammalian U-box proteins, in conjunction with an E1 and an E2, mediate polyubiquitylation in the absence of a HECT type or RING-finger type E3. U-box proteins have thus been defined as a third family of E3s. We here review recent progress in the characterization of U-box proteins and of their role in the quality control system that underlies the cellular stress response to the intracellular accumulation of abnormal proteins.

Original languageEnglish
Pages (from-to)635-645
Number of pages11
JournalBiochemical and Biophysical Research Communications
Issue number4
Publication statusPublished - Mar 21 2003

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


Dive into the research topics of 'U-box proteins as a new family of ubiquitin ligases'. Together they form a unique fingerprint.

Cite this