The Ubiquitin-like Protein FAT10 Stabilizes eEF1A1 Expression to Promote Tumor Proliferation in a Complex Manner.
Human HLA-F adjacent transcript 10 (FAT10) is the only ubiquitin-like protein that can directly target substrates for degradation by proteasomes, but it can also stabilize the expression of certain substrates by antagonizing ubiquitination, through mechanisms as yet uncharacterized. In this study, we show how FAT10 stabilizes the translation elongation factor eEF1A1, which contributes to cancer cell proliferation. FAT10 overexpression increased expression of eEF1A1, which was sufficient to promote proliferation of cancer cells. Mechanistic investigations revealed that FAT10 competed with ubiquitin (Ub) for binding to the same lysines on eEF1A1 to form either FAT10-eEF1A1 or Ub-eEF1A1 complexes, respectively, such that FAT10 overexpression decreased Ub-eEF1A1 levels and increased FAT10-eEF1A1 levels. Overall, our work establishes a novel mechanism through which FAT10 stabilizes its substrates, advancing understanding of the biological function of FAT10 and its role in cancer. Cancer Res; 76(16); 4897-907. ©2016 AACR.
Department of General Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, China. Jiangxi Province Key Laboratory of Molecular Medicine, Nanchang, China.
Xiuxia
X
Liu
Department of General Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, China. Jiangxi Province Key Laboratory of Molecular Medicine, Nanchang, China. Jiangxi Province Engineering Research Center of Hepatobiliary Disease, Nanchang, China.
Leifeng
L
Chen
Department of General Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, China. Jiangxi Province Key Laboratory of Molecular Medicine, Nanchang, China. Jiangxi Province Engineering Research Center of Hepatobiliary Disease, Nanchang, China.
Jin
J
Ge
Department of General Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, China. Jiangxi Province Engineering Research Center of Hepatobiliary Disease, Nanchang, China.
Chen
C
Yan
Department of General Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, China. Jiangxi Province Key Laboratory of Molecular Medicine, Nanchang, China.
Zixi
Z
Huang
Department of General Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, China.
Junwen
J
Hu
Department of General Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, China. Jiangxi Province Key Laboratory of Molecular Medicine, Nanchang, China. Jiangxi Province Engineering Research Center of Hepatobiliary Disease, Nanchang, China.
Chongyu
C
Wen
Department of General Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, China. Jiangxi Province Key Laboratory of Molecular Medicine, Nanchang, China. Jiangxi Province Engineering Research Center of Hepatobiliary Disease, Nanchang, China.
Ming
M
Li
Department of General Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, China. Jiangxi Province Key Laboratory of Molecular Medicine, Nanchang, China. Jiangxi Province Engineering Research Center of Hepatobiliary Disease, Nanchang, China.
Da
D
Huang
Department of General Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, China. Jiangxi Province Key Laboratory of Molecular Medicine, Nanchang, China. Jiangxi Province Engineering Research Center of Hepatobiliary Disease, Nanchang, China.
Yumin
Y
Qiu
Department of General Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, China. Jiangxi Province Key Laboratory of Molecular Medicine, Nanchang, China. Jiangxi Province Engineering Research Center of Hepatobiliary Disease, Nanchang, China.
Haibin
H
Hao
Department of General Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, China. Jiangxi Province Engineering Research Center of Hepatobiliary Disease, Nanchang, China.
Rongfa
R
Yuan
Department of General Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, China. Jiangxi Province Engineering Research Center of Hepatobiliary Disease, Nanchang, China.
Jun
J
Lei
Department of General Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, China. Jiangxi Province Engineering Research Center of Hepatobiliary Disease, Nanchang, China.
Xin
X
Yu
Department of General Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, China. Jiangxi Province Key Laboratory of Molecular Medicine, Nanchang, China. Jiangxi Province Engineering Research Center of Hepatobiliary Disease, Nanchang, China. shao5022@163.com.
Jianghua
J
Shao
D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation; D064593:Heterografts; D006801:Humans; D047468:Immunoprecipitation; D051379:Mice; D008819:Mice, Nude; D018613:Microscopy, Confocal; D016297:Mutagenesis, Site-Directed; D009374:Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology*; D020648:Peptide Elongation Factor 1 / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D025801:Ubiquitin / Q000378:metabolism; D054875:Ubiquitination; D014452:Ubiquitins / Q000378:metabolism*
C094814:EEF1A1 protein, human; D020648:Peptide Elongation Factor 1; C109184:UBD protein, human; D025801:Ubiquitin; D014452:Ubiquitins