title: CHIP/Stub1 interacts with eIF5A and mediates its degradation.
abstract: 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.
authors: The Key Laboratory for Cell Proliferation and Regulation Biology of Ministry of Education, College of Life Sciences, Beijing Normal University, Beijing 100875, China; State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Medicine, Tsinghua University, Beijing 100084, China. Electronic address: shangyu@bnu.edu.cn.
authors: Yu
authors: Y
authors: Shang
authors: State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Medicine, Tsinghua University, Beijing 100084, China; State Key Laboratory of Pathogens and Biosecurity, Laboratory of Applied Molecular Biology, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
authors: Xinghui
authors: X
authors: Zhao
authors: Department of Surgical Oncology, Affiliated Hospital of Shaanxi University of Chinese Medicine, Shaanxi, Xianyang 712083, China.
authors: Bo
authors: B
authors: Tian
authors: State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Medicine, Tsinghua University, Beijing 100084, China.
authors: Yinyin
authors: Y
authors: Wang
authors: State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Medicine, Tsinghua University, Beijing 100084, China.
authors: Fangli
authors: F
authors: Ren
authors: Department of General Surgery, Chinese PLA General Hospital, Beijing 100853, China.
authors: Baoqing
authors: B
authors: Jia
authors: The Key Laboratory for Cell Proliferation and Regulation Biology of Ministry of Education, College of Life Sciences, Beijing Normal University, Beijing 100875, China.
authors: Yonggong
authors: Y
authors: Zhai
authors: State Key Laboratory of Pathogens and Biosecurity, Laboratory of Applied Molecular Biology, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
authors: Wei
authors: W
authors: Chen
authors: The Key Laboratory for Cell Proliferation and Regulation Biology of Ministry of Education, College of Life Sciences, Beijing Normal University, Beijing 100875, China.
authors: Dacheng
authors: D
authors: He
authors: State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Medicine, Tsinghua University, Beijing 100084, China. Electronic address: zhijiec@tsinghua.edu.cn.
authors: Zhijie
authors: Z
authors: Chang
mesh_terms: D000818:Animals; D002460:Cell Line; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D010448:Peptide Initiation Factors / Q000378:metabolism*; D011485:Protein Binding; D055550:Protein Stability; D040901:Proteomics; D016601:RNA-Binding Proteins / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination; D000097574:Eukaryotic Translation Initiation Factor 5A
chemical_list: D010448:Peptide Initiation Factors; D016601:RNA-Binding Proteins; D044767:Ubiquitin-Protein Ligases; D000097574:Eukaryotic Translation Initiation Factor 5A; C467728:STUB1 protein, human
keywords: CHIP/Stub1; Colorectal cancer; E3 ligase; Protein–protein interaction; eIF5A degradation