TY - JOUR
T1 - Cullin-3/KCTD10 complex is essential for K27-polyubiquitination of EIF3D in human hepatocellular carcinoma HepG2 cells
AU - Maekawa, Masashi
AU - Hiyoshi, Hiromi
AU - Nakayama, Jun
AU - Kido, K.
AU - Sawasaki, Tatsuya
AU - Semba, Kentaro
AU - Kubota, Eiji
AU - Joh, Takashi
AU - Higashiyama, Shigeki
N1 - Funding Information:
This work was supported by JSPS KAKENHI (Grant Numbers 18K15244 to M.M. and JP16H046980 to S.H.) and Takeda Science Foundation (Research grant to Proteo-Science Center). We thank Ms. Ayako Fujisaki, Ms. Mami Chosei, and Dr. Tomohisa Sakaue (Ehime University) for their technical assistance. We also thank Dr. Atsuo T. Sasaki (University of Cincinnati College of Medicine) for providing the HA-tagged ubiquitin (wild-type, K48, and K63) plasmids. This work was partially supported by The Yasuda Medical Foundation.
Funding Information:
This work was supported by JSPS KAKENHI (Grant Numbers 18K15244 to M.M. and JP16H046980 to S.H.) and Takeda Science Foundation (Research grant to Proteo-Science Center).
Funding Information:
We thank Ms. Ayako Fujisaki, Ms. Mami Chosei, and Dr. Tomohisa Sakaue (Ehime University) for their technical assistance. We also thank Dr. Atsuo T. Sasaki (University of Cincinnati College of Medicine) for providing the HA-tagged ubiquitin (wild-type, K48, and K63) plasmids. This work was partially supported by The Yasuda Medical Foundation.
Publisher Copyright:
© 2019 The Authors
PY - 2019/9/3
Y1 - 2019/9/3
N2 - 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.
AB - 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.
KW - Cullin-3 (CUL3)
KW - EIF3D
KW - Hepatocellular carcinoma
KW - KCTD10
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U2 - 10.1016/j.bbrc.2019.07.010
DO - 10.1016/j.bbrc.2019.07.010
M3 - Article
C2 - 31280863
AN - SCOPUS:85068390082
SN - 0006-291X
VL - 516
SP - 1116
EP - 1122
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 4
ER -
