PMID- 30857853
OWN - NLM
STAT- MEDLINE
DCOM- 20200424
LR  - 20220129
IS  - 1673-8527 (Print)
IS  - 1673-8527 (Linking)
VI  - 46
IP  - 2
DP  - 2019 Feb
TI  - mTOR-S6K1 pathway mediates cytoophidium assembly.
PG  - 65-74
LID - S1673-8527(19)30018-9 [pii]
LID - 10.1016/j.jgg.2018.11.006 [doi]
AB  - CTP synthase (CTPS), the rate-limiting enzyme in de novo CTP biosynthesis, has 
      been demonstrated to assemble into evolutionarily conserved filamentous 
      structures, termed cytoophidia, in Drosophila, bacteria, yeast and mammalian 
      cells. However, the regulation and function of the cytoophidium remain elusive. 
      Here, we provide evidence that the mechanistic target of rapamycin (mTOR) pathway 
      controls cytoophidium assembly in mammalian and Drosophila cells. In mammalian 
      cells, we find that inhibition of mTOR pathway attenuates cytoophidium formation. 
      Moreover, CTPS cytoophidium assembly appears to be dependent on the mTOR complex 
      1 (mTORC1) mainly. In addition, knockdown of the mTORC1 downstream target S6K1 
      can inhibit cytoophidium formation, while overexpression of the constitutively 
      active S6K1 reverses mTOR knockdown-induced cytoophidium disassembly. Finally, 
      reducing mTOR protein expression results in a decrease of the length of 
      cytoophidium in Drosophila follicle cells. Therefore, our study connects CTPS 
      cytoophidium formation with the mTOR signaling pathway.
CI  - Copyright (c) 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.
FAU - Sun, Zhe
AU  - Sun Z
AD  - School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, 
      China.
FAU - Liu, Ji-Long
AU  - Liu JL
AD  - School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, 
      China; MRC Functional Genomics Unit, Department of Physiology, Anatomy and 
      Genetics, University of Oxford, Oxford, OX1 3PT, United Kingdom. Electronic 
      address: liujl3@shanghaitech.edu.cn.
LA  - eng
GR  - MC_U137788471/MRC_/Medical Research Council/United Kingdom
GR  - MC_UU_12021/3/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190131
PL  - China
TA  - J Genet Genomics
JT  - Journal of genetics and genomics = Yi chuan xue bao
JID - 101304616
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (ribosomal protein S6 kinase, 70kD, polypeptide 1)
RN  - EC 6.3.- (Carbon-Nitrogen Ligases)
RN  - EC 6.3.4.2 (CTP synthetase)
SB  - IM
MH  - Animals
MH  - Carbon-Nitrogen Ligases/chemistry/*metabolism
MH  - Cell Line, Tumor
MH  - Cytoplasm/metabolism
MH  - Drosophila melanogaster/*cytology/enzymology/metabolism
MH  - Humans
MH  - Protein Multimerization
MH  - Protein Structure, Quaternary
MH  - Ribosomal Protein S6 Kinases, 70-kDa/*metabolism
MH  - *Signal Transduction
MH  - TOR Serine-Threonine Kinases/*metabolism
PMC - PMC6459811
OTO - NOTNLM
OT  - CTP synthase
OT  - Colorectal cancer cell
OT  - Cytoophidium
OT  - Drosophila
OT  - mTOR
EDAT- 2019/03/13 06:00
MHDA- 2020/04/25 06:00
PMCR- 2019/02/01
CRDT- 2019/03/13 06:00
PHST- 2018/08/04 00:00 [received]
PHST- 2018/11/21 00:00 [revised]
PHST- 2018/11/30 00:00 [accepted]
PHST- 2019/03/13 06:00 [pubmed]
PHST- 2020/04/25 06:00 [medline]
PHST- 2019/03/13 06:00 [entrez]
PHST- 2019/02/01 00:00 [pmc-release]
AID - S1673-8527(19)30018-9 [pii]
AID - 10.1016/j.jgg.2018.11.006 [doi]
PST - ppublish
SO  - J Genet Genomics. 2019 Feb;46(2):65-74. doi: 10.1016/j.jgg.2018.11.006. Epub 2019 
      Jan 31.