CHIP/Stub1 interacts with elF5A and mediates its degradation

elF5A, containing the unusual amino acid hypusine, is a highly conserved protein essential for the proliferation of eukaryotic cells. Previous studies have demonstrated that the activity of eIF5A was regulated through modification of hypusine, phosphorylation and acetylation. However, no study was documented for regulation of the protein stability. Here, we report that eIF5A is a target of CHIP (the carboxyl terminus of Hsc70-interacting protein, also named Stub1), an E3 ligase with a U-box domain, through a proteomics analysis. CHIP directly interacted with eIF5A, preferably through the U-box domain, to mediate elF5A ubiquitination and degradation. Simultaneously, we investigated that CHIP expression inversely correlated with elF5A levels in colorectal cancers, consistent with the fact that the protein level of elF5A was increased in the CHIP knock-out MEF cells. Taken together, we propose that CHIP regulates the elF5A protein stability via a protein degradation mechanism. This study provides a new insight into understanding the regulation of the elF5A stability. (C) 2014 Elsevier Inc All rights reserved.