PMID- 30566892
OWN - NLM
STAT- MEDLINE
DCOM- 20190909
LR  - 20200309
IS  - 1873-2968 (Electronic)
IS  - 0006-2952 (Print)
IS  - 0006-2952 (Linking)
VI  - 160
DP  - 2019 Feb
TI  - RNA interference screen identifies NAA10 as a regulator of PXR transcription.
PG  - 92-109
LID - S0006-2952(18)30511-2 [pii]
LID - 10.1016/j.bcp.2018.12.012 [doi]
AB  - The pregnane X receptor (PXR) is a principal xenobiotic receptor crucial in the 
      detection, detoxification, and clearance of toxic substances from the body. PXR 
      plays a vital role in the metabolism and disposition of drugs, and elevated PXR 
      levels contribute to cancer drug resistance. Therefore, to modulate PXR activity 
      and mitigate drug resistance, it is imperative to fully understand its 
      regulation. To this end, we screened a transcription factor siRNA library in 
      pancreatic cancer cells that express high levels of PXR. Through a comprehensive 
      deconvolution process, we identified N-alpha-acetyltransferase 10 (NAA10) as a 
      factor in the transcriptional machinery regulating PXR transcription. Because no 
      one single factor has 100% operational control of PXR transcriptional regulation, 
      our results together with other previous findings suggest that the 
      transcriptional regulation of PXR is complex and that multiple factors contribute 
      to the process including NAA10.
CI  - Copyright (c) 2018 Elsevier Inc. All rights reserved.
FAU - Oladimeji, Peter O
AU  - Oladimeji PO
AD  - Department of Chemical Biology and Therapeutics, St. Jude Children's Research 
      Hospital, Memphis, TN 38105, United States.
FAU - Wright, William C
AU  - Wright WC
AD  - Department of Chemical Biology and Therapeutics, St. Jude Children's Research 
      Hospital, Memphis, TN 38105, United States; Integrated Biomedical Sciences 
      Program, University of Tennessee Health Science Center, Memphis, TN 38163, United 
      States.
FAU - Wu, Jing
AU  - Wu J
AD  - Department of Chemical Biology and Therapeutics, St. Jude Children's Research 
      Hospital, Memphis, TN 38105, United States.
FAU - Chen, Taosheng
AU  - Chen T
AD  - Department of Chemical Biology and Therapeutics, St. Jude Children's Research 
      Hospital, Memphis, TN 38105, United States; Integrated Biomedical Sciences 
      Program, University of Tennessee Health Science Center, Memphis, TN 38163, United 
      States. Electronic address: taosheng.chen@stjude.org.
LA  - eng
GR  - P30 CA021765/CA/NCI NIH HHS/United States
GR  - R01 GM110034/GM/NIGMS NIH HHS/United States
GR  - R35 GM118041/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20181216
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (Antibiotics, Antineoplastic)
RN  - 0 (Pregnane X Receptor)
RN  - 80168379AG (Doxorubicin)
RN  - EC 2.3.1.254 (N-Terminal Acetyltransferase A)
RN  - EC 2.3.1.255 (NAA10 protein, human)
RN  - EC 2.3.1.258 (N-Terminal Acetyltransferase E)
SB  - IM
MH  - Antibiotics, Antineoplastic/pharmacology
MH  - Cell Line, Tumor
MH  - Doxorubicin/pharmacology
MH  - Gene Expression Regulation, Neoplastic/drug effects/*genetics
MH  - Humans
MH  - N-Terminal Acetyltransferase A/*genetics/metabolism
MH  - N-Terminal Acetyltransferase E/*genetics/metabolism
MH  - Pregnane X Receptor/*genetics/metabolism
MH  - Promoter Regions, Genetic/genetics
MH  - Protein Binding
MH  - *RNA Interference
PMC - PMC6361121
MID - NIHMS1516831
OTO - NOTNLM
OT  - Gene expression
OT  - PXR
OT  - Transcriptional regulation
OT  - Xenobiotic receptor
COIS- CONFLICT OF INTEREST The authors declare no competing financial interests.
EDAT- 2018/12/20 06:00
MHDA- 2019/09/10 06:00
PMCR- 2020/02/01
CRDT- 2018/12/20 06:00
PHST- 2018/10/30 00:00 [received]
PHST- 2018/12/14 00:00 [accepted]
PHST- 2018/12/20 06:00 [pubmed]
PHST- 2019/09/10 06:00 [medline]
PHST- 2018/12/20 06:00 [entrez]
PHST- 2020/02/01 00:00 [pmc-release]
AID - S0006-2952(18)30511-2 [pii]
AID - 10.1016/j.bcp.2018.12.012 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 2019 Feb;160:92-109. doi: 10.1016/j.bcp.2018.12.012. Epub 2018 
      Dec 16.