PMID- 34171383
OWN - NLM
STAT- MEDLINE
DCOM- 20210810
LR  - 20210810
IS  - 1879-0631 (Electronic)
IS  - 0024-3205 (Linking)
VI  - 281
DP  - 2021 Sep 15
TI  - Analysis of the mTOR Interactome using SILAC technology revealed NICE-4 as a 
      novel regulator of mTORC1 activity.
PG  - 119745
LID - S0024-3205(21)00731-1 [pii]
LID - 10.1016/j.lfs.2021.119745 [doi]
AB  - The evolutionarily conserved mechanistic target of rapamycin (mTOR) forms two 
      functionally distinct complexes, -the mTOR complex 1 (mTORC1) and mTOR complex 2 
      (mTORC2)-which differ in their subunit composition. Although the function of 
      mTORC1 has been studied extensively, the interaction between mTORC1 and the 
      ubiquitin-proteasome system (UPS) remains unclear. To facilitate a thorough 
      understanding of the mechanismby which UPS regulates mTORC1 activity, steady 
      isotope labeling with amino acids in cell culture (SILAC) technology was used to 
      screen for potential mTORC1-interacting UPS members. Fourteen previously unknown 
      proteins bound to mTOR in HEK293 cells with a SILAC ratio (heavy/light, H/L) 
      above 2, five of which are components of the UPS. Subsequent immunoprecipitation 
      analysis confirmed that ubiquitin-relevant protein 2-like (UBAP2L, also known as 
      NICE-4) binds to both mTOR and Raptor, but not Rictor, suggesting that NICE-4 
      specifically interacts with mTORC1, but not mTORC2. Interestingly, NICE-4 is 
      essential for basic mTORC1 activity in both HeLa cancer cells and HEK293 cells. 
      In addition, NICE-4 depletion markedly suppressed proliferation of both HeLa and 
      HEK293 cells as well as survival of HeLa cells. Collectively, these results 
      revealed the identity of novel mTOR-interacting UPS proteins and established 
      NICE-4 as a critical UPS member that maintains mTORC1 activity.
CI  - Copyright (c) 2021 Elsevier Inc. All rights reserved.
FAU - Wang, Yun
AU  - Wang Y
AD  - Department of Cell Biology, School of Basic Medical Sciences, Southern Medical 
      University, Guangzhou 510515, Guangdong, China. Electronic address: 
      wangyun12@foxmai.com.
FAU - Chen, Zhenguo
AU  - Chen Z
AD  - Department of Cell Biology, School of Basic Medical Sciences, Southern Medical 
      University, Guangzhou 510515, Guangdong, China. Electronic address: 
      czg1984@smu.edu.cn.
FAU - Jia, Chunhong
AU  - Jia C
AD  - Department of Cell Biology, School of Basic Medical Sciences, Southern Medical 
      University, Guangzhou 510515, Guangdong, China.
FAU - Bai, Xiaochun
AU  - Bai X
AD  - Department of Cell Biology, School of Basic Medical Sciences, Southern Medical 
      University, Guangzhou 510515, Guangdong, China. Electronic address: 
      baixc15@smu.edu.cn.
FAU - Jiang, Yu
AU  - Jiang Y
AD  - Department of Pharmacology and Chemical Biology, University of Pittsburgh School 
      of Medicine, PA 15213, USA. Electronic address: yuj5@pitt.edu.
FAU - Zou, Zhipeng
AU  - Zou Z
AD  - Department of Cell Biology, School of Basic Medical Sciences, Southern Medical 
      University, Guangzhou 510515, Guangdong, China. Electronic address: 
      zzp@smu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20210623
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (Ubiquitin)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
SB  - IM
MH  - Cell Death
MH  - Cell Proliferation
MH  - HEK293 Cells
MH  - HeLa Cells
MH  - Humans
MH  - Mass Spectrometry/methods
MH  - Mechanistic Target of Rapamycin Complex 1/*metabolism
MH  - Proteasome Endopeptidase Complex/metabolism
MH  - Protein Binding
MH  - Ubiquitin/metabolism
OTO - NOTNLM
OT  - Cancer
OT  - HeLa cells
OT  - NICE-4
OT  - SILAC
OT  - Ubiquitin-proteasome system
OT  - mTORC1
EDAT- 2021/06/26 06:00
MHDA- 2021/08/11 06:00
CRDT- 2021/06/25 20:12
PHST- 2021/01/06 00:00 [received]
PHST- 2021/06/15 00:00 [revised]
PHST- 2021/06/15 00:00 [accepted]
PHST- 2021/06/26 06:00 [pubmed]
PHST- 2021/08/11 06:00 [medline]
PHST- 2021/06/25 20:12 [entrez]
AID - S0024-3205(21)00731-1 [pii]
AID - 10.1016/j.lfs.2021.119745 [doi]
PST - ppublish
SO  - Life Sci. 2021 Sep 15;281:119745. doi: 10.1016/j.lfs.2021.119745. Epub 2021 Jun 
      23.