title: Altered activity patterns of transcription factors induced by endoplasmic reticulum stress.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Signosis Inc., 1700 Wyatt Drive, Suite #10-12, Santa Clara, CA, 95054, USA.
authors.forename: Sheena
authors.initials: S
authors.lastname: Jiang
authors.affiliation: Saratoga High School, 20300 Herriman Ave, Saratoga, CA, 95070, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Zhang
authors.affiliation: Saratoga High School, 20300 Herriman Ave, Saratoga, CA, 95070, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Signosis Inc., 1700 Wyatt Drive, Suite #10-12, Santa Clara, CA, 95054, USA. jasonli@signosisinc.com.
authors.forename: Xianqiang
authors.initials: X
authors.lastname: Li
mesh_terms: D045744:Cell Line, Tumor; D024202:Electrophoretic Mobility Shift Assay; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter; D006801:Humans; D015398:Signal Transduction / Q000187:drug effects; D019284:Thapsigargin / Q000633:toxicity; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D014415:Tunicamycin / Q000633:toxicity
chemical_list: D014157:Transcription Factors; D014415:Tunicamycin; D019284:Thapsigargin
keywords: Activation and Signal pathways; ER stress; Plate array; TF; UPR