Inhibition of ubiquitin-proteasome pathway–mediated IκBα degradation by a naturally occurring antibacterial peptide

• DOI: 10.1172/jci9826
• Publication Date: 2008-02-19T19:15:54Z
• Authors: Youhe Gao; Stewart Lecker; Mark J. Post; Antti J. Hietaranta; Jian Li; Rudiger Volk; Min Li; Kaori Sato; Ashok K. Saluja; Michael L. Steer; Alfred L. Goldberg; Michael Simons
• Keywords: Protein Degradation; F-box protein

Induction of NF-κB–dependent gene expression plays an important role in a number biological processes including inflammation and ischemia-reperfusion injury. However, few attempts aimed at selective regulation this transcription factor have been successful. We report here that naturally occurring antibacterial peptide PR39 reversibly binds to the α7 subunit 26S proteasome blocks degradation NF-κB inhibitor IκBα by ubiquitin-proteasome pathway without affecting overall activity. phosphorylation ubiquitination occur normally after treatment, binding valosin-containing proteins is not impaired. The inhibition abolishes induction cell culture mouse models acute pancreatitis myocardial infarction, upregulation endothelial adhesion VCAM-1 ICAM-1. In latter model, sustained infusion resulted significant reduction infarct size. related peptides may provide novel means regulate cellular function control for therapeutic purposes.