PMID- 36587526
OWN - NLM
STAT- MEDLINE
DCOM- 20230124
LR  - 20231116
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 643
DP  - 2023 Feb 5
TI  - Chromatin remodeler BRM is a key mediator of leucine-stimulated mTOR gene 
      transcription in mouse mammary epithelial cells.
PG  - 88-95
LID - S0006-291X(22)01735-1 [pii]
LID - 10.1016/j.bbrc.2022.12.064 [doi]
AB  - Brahma (BRM) is one of the core ATPase subunits of SWI/SNF chromatin remodeling 
      complex, and participates in various important cellular regulatory processes. 
      However, the role of BRM in regulating gene expression of the mechanistic target 
      of rapamycin (mTOR) still remains unknown. In this study, we explored the effects 
      and the corresponding molecular mechanisms of BRM on Leucine (Leu)-stimulated 
      mTOR activation in and proliferation of a mouse mammary epithelial cell (MEC) 
      line (HC11 cell). Initially, we found that the abundance of BRM protein in 
      mammary gland tissue during lactation was significantly higher than that during 
      puberty and involution. BRM knockdown inhibited HC11 cell proliferation, mRNA 
      expression of mTOR and subsequent protein phosphorylation, whereas BRM gene 
      activation had the opposite effect. Leu affected the level of BRM protein and 
      mTOR phospphorylation in a dose-dependent manner, and BRM knockdown totally 
      blocked the stimulation of Leu on mTOR mRNA expression and protein 
      phospphorylation. ChIP-PCR detected that BRM was bound to the -4368  approximately  -4591 bp 
      site of the mTOR promoter, and ChIP-qPCR further detected that Leu stimulated BRM 
      to bind to this site. In conclusion, these data reveal that BRM is a positive 
      regulator of HC11 cell proliferation and mediates Leu's stimulation on mTOR gene 
      transcription and protein phosphorylation. Our data provide a new theoretical 
      basis for the involvement of BRM in cell proliferation and regulation of the mTOR 
      signaling pathway.
CI  - Copyright (c) 2022 Elsevier Inc. All rights reserved.
FAU - Ke, Changping
AU  - Ke C
AD  - College of Animal Science, Yangtze University, Jingzhou, 434025, China.
FAU - Zhao, Sunqi
AU  - Zhao S
AD  - College of Animal Science, Yangtze University, Jingzhou, 434025, China.
FAU - Wang, Lulu
AU  - Wang L
AD  - College of Animal Science, Yangtze University, Jingzhou, 434025, China.
FAU - Zhang, Minghui
AU  - Zhang M
AD  - College of Animal Science, Yangtze University, Jingzhou, 434025, China. 
      Electronic address: minghuizhang2019@163.com.
FAU - Gao, Xuejun
AU  - Gao X
AD  - College of Animal Science, Yangtze University, Jingzhou, 434025, China. 
      Electronic address: gaoxj53901@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20221226
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Chromatin)
RN  - 0 (Transcription Factors)
RN  - GMW67QNF9C (Leucine)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - Female
MH  - Animals
MH  - Mice
MH  - *Chromatin/metabolism
MH  - *Transcription Factors/metabolism
MH  - Leucine/pharmacology/metabolism
MH  - Sexual Maturation
MH  - Epithelial Cells/metabolism
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Transcription, Genetic
MH  - RNA, Messenger/metabolism
OTO - NOTNLM
OT  - BRM
OT  - Leucine
OT  - Mammary epithelial cell
OT  - Proliferation
OT  - mTOR
COIS- Declaration of competing interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2023/01/02 06:00
MHDA- 2023/01/25 06:00
CRDT- 2023/01/01 18:11
PHST- 2022/12/11 00:00 [received]
PHST- 2022/12/21 00:00 [accepted]
PHST- 2023/01/02 06:00 [pubmed]
PHST- 2023/01/25 06:00 [medline]
PHST- 2023/01/01 18:11 [entrez]
AID - S0006-291X(22)01735-1 [pii]
AID - 10.1016/j.bbrc.2022.12.064 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2023 Feb 5;643:88-95. doi: 
      10.1016/j.bbrc.2022.12.064. Epub 2022 Dec 26.