The tight junction-specific protein occludin is a functional target of the E3 ubiquitin-protein ligase itch

Andreas Traweger, Deyu Fang, Yun Cai Liu, Wolfgang Stelzhammer, István A. Krizbai, Fritz Fresser, Hans Christian Bauer*, Hannelore Bauer

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

162 Scopus citations


Tight junctions create a highly selective diffusion barrier between epithelial and endothelial cells by preventing the free passage of molecules and ions across the paracellular pathway. Although the regulation of this barrier is still enigmatic, there is evidence that junctional transmembrane proteins are critically involved. Recent evidence confirms the notion that occludin, a four-pass integral plasma-membrane protein, is a functional component of the paracellular barrier. The overall hydrophilicity of occludin predicts two extracellular loops bounded by NH2- and COOH-terminal cytoplasmic domains. To date, the binding of the COOH terminus of occludin to intracellular proteins is well documented, but information concerning the function of the cytoplasmic NH2 terminus is still lacking. Using yeast two-hybrid screening we have identified a novel interaction between occludin and the E3 ubiquitin-protein ligase Itch, a member of the HECT domain-containing ubiquitin-protein ligases. We have found that the NH2-terminal portion of occludin binds specifically to a multidomain of Itch, consisting of four WW motifs. This interaction has been confirmed by our results from in vivo and in vitro co-immunoprecipitation experiments. In addition, we provide evidence that Itch is specifically involved in the ubiquitination of occludin in vivo, and that the degradation of occludin is sensitive to proteasome inhibition.

Original languageEnglish (US)
Pages (from-to)10201-10208
Number of pages8
JournalJournal of Biological Chemistry
Issue number12
StatePublished - Mar 22 2002

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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