Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P50502 (Hip)
 7,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

eIF5A, 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 eIF5A ubiquitination and degradation. Simultaneously, we investigated that CHIP expression inversely correlated with eIF5A levels in colorectal cancers, consistent with the fact that the protein level of eIF5A was increased in the CHIP knock-out MEF cells. Taken together, we propose that CHIP regulates the eIF5A protein stability via a protein degradation mechanism. This study provides a new insight into understanding the regulation of the eIF5A stability.
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PMID:CHIP/Stub1 interacts with eIF5A and mediates its degradation. 2450 16