STUB1-mediated ubiquitination regulates the stability of GLUD1 in lung adenocarcinoma
Qifan Hu,
Jiapeng Lei,
Zhujun Cheng,
Jing Xu,
Lei Wang,
Yi Yuan,
Mingxi Gan,
Yanan Wang,
Yilin Xie,
Lu Yao,
Keru Wang,
Yuhan Liu,
Wenze Xun,
Jian-Bin Wang,
Tianyu Han
Affiliations
Qifan Hu
Jiangxi Institute of Respiratory Disease, The First Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi 330006, China; School of Basic Medical Sciences, Nanchang University, Nanchang City, Jiangxi 330031, China; Department of Thoracic Surgery, The First Affifiliated Hospital of Nanchang University, Nanchang City, Jiangxi 330006, China
Jiapeng Lei
School of Basic Medical Sciences, Nanchang University, Nanchang City, Jiangxi 330031, China; School of Basic Medical Sciences, Nanchang Medical College, Nanchang City, Jiangxi 330000, China
Zhujun Cheng
Department of Burn, The First Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi 330006, China
Jing Xu
School of Basic Medical Sciences, Nanchang University, Nanchang City, Jiangxi 330031, China
Lei Wang
School of Basic Medical Sciences, Nanchang University, Nanchang City, Jiangxi 330031, China
Yi Yuan
School of Huankui Academy, Nanchang University, Nanchang City, Jiangxi 330031, China
Mingxi Gan
School of Basic Medical Sciences, Nanchang University, Nanchang City, Jiangxi 330031, China
Yanan Wang
Jiangxi Institute of Respiratory Disease, The First Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi 330006, China
Yilin Xie
School of Queen Mary, Nanchang University, Nanchang City, Jiangxi 330031, China
Lu Yao
School of Huankui Academy, Nanchang University, Nanchang City, Jiangxi 330031, China
Keru Wang
School of Huankui Academy, Nanchang University, Nanchang City, Jiangxi 330031, China
Yuhan Liu
School of Basic Medical Sciences, Nanchang University, Nanchang City, Jiangxi 330031, China
Wenze Xun
School of Basic Medical Sciences, Nanchang University, Nanchang City, Jiangxi 330031, China
Jian-Bin Wang
School of Basic Medical Sciences, Nanchang University, Nanchang City, Jiangxi 330031, China; Department of Thoracic Surgery, The First Affifiliated Hospital of Nanchang University, Nanchang City, Jiangxi 330006, China
Tianyu Han
Jiangxi Institute of Respiratory Disease, The First Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi 330006, China; Jiangxi Clinical Research Center for Respiratory Diseases, Nanchang City, Jiangxi 330006, China; China-Japan Friendship Jiangxi Hospital, National Regional Center for Respiratory Medicine, Nanchang City, Jiangxi 330200, China; Corresponding author
Summary: The dysregulation of glutamine metabolism provides survival advantages for tumors by supplementing tricarboxylic acid cycle. Glutamate dehydrogenase 1 (GLUD1) is one of the key enzymes in glutamine catabolism. Here, we found that enhanced protein stability was the key factor for the upregulation of GLUD1 in lung adenocarcinoma. We discovered that GLUD1 showed a high protein expression in lung adenocarcinoma cells or tissues. We elucidated that STIP1 homology and U-box-containing protein 1 (STUB1) was the key E3 ligase responsible for ubiquitin-mediated proteasomal degradation of GLUD1. We further showed that lysine 503 (K503) was the main ubiquitination site of GLUD1, inhibiting the ubiquitination at this site promoted the proliferation and tumor growth of lung adenocarcinoma cells. Taken together, this study clarifies the molecular mechanism of GLUD1 in maintaining protein homeostasis in lung adenocarcinoma, which provides a theoretical basis for the development of anti-cancer drugs targeting GLUD1.
