PMID- 27009139
OWN - NLM
STAT- MEDLINE
DCOM- 20161011
LR  - 20181113
IS  - 1471-2091 (Electronic)
IS  - 1471-2091 (Linking)
VI  - 17
DP  - 2016 Mar 24
TI  - Altered activity patterns of transcription factors induced by endoplasmic 
      reticulum stress.
PG  - 8
LID - 10.1186/s12858-016-0060-2 [doi]
LID - 8
AB  - BACKGROUND: The endoplasmic-reticulum (ER) responds to the burden of unfolded 
      proteins in its lumen by activating intracellular signal transduction pathways, 
      also known as the unfolded protein response (UPR). Many signal transduction 
      events and transcription factors have been demonstrated to be associated with ER 
      stress. The process in which ER stress affects or interacts with other pathways 
      is still a progressing topic that is not completely understood. Identifying new 
      transcription factors associated with ER stress pathways provides a platform to 
      comprehensively characterize mechanism and functionality of ER. METHODS: We 
      utilized a transcription factor (TF) activation plate array to profile the TF 
      activities which were affected by ER stress induced by pharmacological agents, 
      thapsigargin (TG) and tunicamycin (TM) at 1 h, 4 h, 8 h and 16 h respectively, in 
      MiaPACA2 cells. The altered activity patterns were analyzed and validated using 
      gel shift assays and cell-based luciferase reporter assay. RESULTS: The study has 
      not only confirmed previous findings, which the TFs including ATF4, ATF6, XBP, 
      NFkB, CHOP and AP1, were activated by ER stress, but also found four newly 
      discovered TFs, NFAT, TCF/LEF were activated, and PXR was repressed in response 
      of ER stress. Different patterns of TF activities in MiaPaCa2 were demonstrated 
      upon TM or TG treatment in the time course experiments. The altered activities of 
      TFs were confirmed using gel shift assays and luciferase reporter vectors. 
      CONCLUSION: This study utilized a TF activation array technology to identify four 
      new TFs, HIF, NFAT, TCF/LEF and PXR that were changed in their activity as a 
      result of ER stress induced by TG and TM. The TF activity patterns were 
      demonstrated to be diverse in response to the duration of TG or TM treatment. 
      These new findings will facilitate further unveiling the complex mechanisms of 
      the ER stress process and associated diseases.
FAU - Jiang, Sheena
AU  - Jiang S
AD  - Signosis Inc., 1700 Wyatt Drive, Suite #10-12, Santa Clara, CA, 95054, USA.
FAU - Zhang, Eric
AU  - Zhang E
AD  - Saratoga High School, 20300 Herriman Ave, Saratoga, CA, 95070, USA.
FAU - Zhang, Rachel
AU  - Zhang R
AD  - Saratoga High School, 20300 Herriman Ave, Saratoga, CA, 95070, USA.
FAU - Li, Xianqiang
AU  - Li X
AD  - Signosis Inc., 1700 Wyatt Drive, Suite #10-12, Santa Clara, CA, 95054, USA. 
      jasonli@signosisinc.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160324
PL  - England
TA  - BMC Biochem
JT  - BMC biochemistry
JID - 101084098
RN  - 0 (Transcription Factors)
RN  - 11089-65-9 (Tunicamycin)
RN  - 67526-95-8 (Thapsigargin)
SB  - IM
MH  - Cell Line, Tumor
MH  - Electrophoretic Mobility Shift Assay
MH  - *Endoplasmic Reticulum Stress/drug effects/genetics
MH  - Gene Expression Regulation/drug effects
MH  - Genes, Reporter
MH  - Humans
MH  - Signal Transduction/drug effects
MH  - Thapsigargin/toxicity
MH  - Transcription Factors/*genetics/*metabolism
MH  - Tunicamycin/toxicity
PMC - PMC4806502
OTO - NOTNLM
OT  - Activation and Signal pathways
OT  - ER stress
OT  - Plate array
OT  - TF
OT  - UPR
EDAT- 2016/03/25 06:00
MHDA- 2016/10/12 06:00
PMCR- 2016/03/24
CRDT- 2016/03/25 06:00
PHST- 2015/08/10 00:00 [received]
PHST- 2016/03/02 00:00 [accepted]
PHST- 2016/03/25 06:00 [entrez]
PHST- 2016/03/25 06:00 [pubmed]
PHST- 2016/10/12 06:00 [medline]
PHST- 2016/03/24 00:00 [pmc-release]
AID - 10.1186/s12858-016-0060-2 [pii]
AID - 60 [pii]
AID - 10.1186/s12858-016-0060-2 [doi]
PST - epublish
SO  - BMC Biochem. 2016 Mar 24;17:8. doi: 10.1186/s12858-016-0060-2.