Cullin-3/KCTD10 complex is essential for K27-polyubiquitination of EIF3D in human hepatocellular carcinoma HepG2 cells

Masashi Maekawa, Hiromi Hiyoshi, Jun Nakayama, K. Kido, Tatsuya Sawasaki, Kentaro Semba, Eiji Kubota, Takashi Joh, Shigeki Higashiyama

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Eukaryotic translation initiation factor 3 subunit D (EIF3D) binds to the 5′-cap of specific mRNAs, initiating their translation into polypeptides. From a pathological standpoint, EIF3D has been observed to be essential for cell growth in various cancer types, and cancer patients with high EIF3D mRNA levels exhibit poor prognosis, indicating involvement of EIF3D in oncogenesis. In this study, we found, by mass spectrometry, that Cullin-3 (CUL3)/KCTD10 ubiquitin (Ub) ligase forms a complex with EIF3D. We also demonstrated that EIF3D is K27-polyubiquitinated at the lysine 153 and 275 residues in a KCTD10-dependent manner in human hepatocellular carcinoma HepG2 cells. Similar to other cancers, high expression of EIF3D significantly correlated with poor prognosis in hepatocellular carcinoma patients, and depletion of EIF3D drastically suppressed HepG2 cell proliferation. These results indicate that EIF3D is a novel substrate of CUL3/KCTD10 Ub ligase and suggest involvement of K27-polyubiquitinated EIF3D in the development of hepatocellular carcinoma.

Original languageEnglish
Pages (from-to)1116-1122
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume516
Issue number4
DOIs
Publication statusPublished - 2019 Sep 3

Keywords

  • Cullin-3 (CUL3)
  • EIF3D
  • Hepatocellular carcinoma
  • KCTD10

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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