PMID- 37416474
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230718
IS  - 2589-0042 (Electronic)
IS  - 2589-0042 (Linking)
VI  - 26
IP  - 7
DP  - 2023 Jul 21
TI  - STUB1-mediated ubiquitination regulates the stability of GLUD1 in lung 
      adenocarcinoma.
PG  - 107151
LID - 10.1016/j.isci.2023.107151 [doi]
LID - 107151
AB  - 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.
CI  - (c) 2023 The Authors.
FAU - Hu, Qifan
AU  - Hu Q
AD  - Jiangxi Institute of Respiratory Disease, The First Affiliated Hospital of 
      Nanchang University, Nanchang City, Jiangxi 330006, China.
AD  - School of Basic Medical Sciences, Nanchang University, Nanchang City, Jiangxi 
      330031, China.
AD  - Department of Thoracic Surgery, The First Affifiliated Hospital of Nanchang 
      University, Nanchang City, Jiangxi 330006, China.
FAU - Lei, Jiapeng
AU  - Lei J
AD  - School of Basic Medical Sciences, Nanchang University, Nanchang City, Jiangxi 
      330031, China.
AD  - School of Basic Medical Sciences, Nanchang Medical College, Nanchang City, 
      Jiangxi 330000, China.
FAU - Cheng, Zhujun
AU  - Cheng Z
AD  - Department of Burn, The First Affiliated Hospital of Nanchang University, 
      Nanchang City, Jiangxi 330006, China.
FAU - Xu, Jing
AU  - Xu J
AD  - School of Basic Medical Sciences, Nanchang University, Nanchang City, Jiangxi 
      330031, China.
FAU - Wang, Lei
AU  - Wang L
AD  - School of Basic Medical Sciences, Nanchang University, Nanchang City, Jiangxi 
      330031, China.
FAU - Yuan, Yi
AU  - Yuan Y
AD  - School of Huankui Academy, Nanchang University, Nanchang City, Jiangxi 330031, 
      China.
FAU - Gan, Mingxi
AU  - Gan M
AD  - School of Basic Medical Sciences, Nanchang University, Nanchang City, Jiangxi 
      330031, China.
FAU - Wang, Yanan
AU  - Wang Y
AD  - Jiangxi Institute of Respiratory Disease, The First Affiliated Hospital of 
      Nanchang University, Nanchang City, Jiangxi 330006, China.
FAU - Xie, Yilin
AU  - Xie Y
AD  - School of Queen Mary, Nanchang University, Nanchang City, Jiangxi 330031, China.
FAU - Yao, Lu
AU  - Yao L
AD  - School of Huankui Academy, Nanchang University, Nanchang City, Jiangxi 330031, 
      China.
FAU - Wang, Keru
AU  - Wang K
AD  - School of Huankui Academy, Nanchang University, Nanchang City, Jiangxi 330031, 
      China.
FAU - Liu, Yuhan
AU  - Liu Y
AD  - School of Basic Medical Sciences, Nanchang University, Nanchang City, Jiangxi 
      330031, China.
FAU - Xun, Wenze
AU  - Xun W
AD  - School of Basic Medical Sciences, Nanchang University, Nanchang City, Jiangxi 
      330031, China.
FAU - Wang, Jian-Bin
AU  - Wang JB
AD  - School of Basic Medical Sciences, Nanchang University, Nanchang City, Jiangxi 
      330031, China.
AD  - Department of Thoracic Surgery, The First Affifiliated Hospital of Nanchang 
      University, Nanchang City, Jiangxi 330006, China.
FAU - Han, Tianyu
AU  - Han T
AD  - Jiangxi Institute of Respiratory Disease, The First Affiliated Hospital of 
      Nanchang University, Nanchang City, Jiangxi 330006, China.
AD  - Jiangxi Clinical Research Center for Respiratory Diseases, Nanchang City, Jiangxi 
      330006, China.
AD  - China-Japan Friendship Jiangxi Hospital, National Regional Center for Respiratory 
      Medicine, Nanchang City, Jiangxi 330200, China.
LA  - eng
PT  - Journal Article
DEP - 20230615
PL  - United States
TA  - iScience
JT  - iScience
JID - 101724038
PMC - PMC10319899
OTO - NOTNLM
OT  - Biological sciences
OT  - Cancer
OT  - Cell biology
OT  - Molecular biology
COIS- The authors declare no competing interests.
EDAT- 2023/07/07 06:42
MHDA- 2023/07/07 06:43
PMCR- 2023/06/15
CRDT- 2023/07/07 04:06
PHST- 2022/12/05 00:00 [received]
PHST- 2023/05/03 00:00 [revised]
PHST- 2023/06/12 00:00 [accepted]
PHST- 2023/07/07 06:43 [medline]
PHST- 2023/07/07 06:42 [pubmed]
PHST- 2023/07/07 04:06 [entrez]
PHST- 2023/06/15 00:00 [pmc-release]
AID - S2589-0042(23)01228-2 [pii]
AID - 107151 [pii]
AID - 10.1016/j.isci.2023.107151 [doi]
PST - epublish
SO  - iScience. 2023 Jun 15;26(7):107151. doi: 10.1016/j.isci.2023.107151. eCollection 
      2023 Jul 21.