Project description:Heat shock transcription factor 1(HSF1) is an important transcription factor which regulates the expression of a wide array of genes including heat shock proteins and oncogenes. Here, we report that HSF1 as a target of WNT/β-catenin signaling, regulates parts of target genes of WNT/β-catenin signaling. To explore the biological relevance of HSF1 activation to WNT/β-catenin signaling, we profiled gene expression of wild type mouse embryonic fibroblasts (WT MEF) and HSF1 knock out MEF (HSF1 KO MEF) before and after lithium chloride (LiCl) treatment which was a potent GSK3β inhibitor and increased the expression of β-catenin.
Project description:Upon heat shock, Hsf1 protein is extensively phosphorylated, however, this modification is inhibited by an hsf1-bal mutation. To get genome-wide effect of the hyperphosphorylation on Hsf1-regulated transcription, the heat-induced gene expression profiles in HSF1 and hsf1-bal cells were compared. Keywords: stress response
Project description:Effect of hsf1-R206S/F256S mutation on heat-induced transcription of genes is analyzed. Total RNA was isolated from HSF1 wild type and hsf1-R206S/F256S cells grown at 39oC for 15 min. Probe cDNA was primed by oligo(dT) and was synthesized in the presence of 33P-dCTP. Hybridization was carried out using the same GF100 GeneFilter. Value higher than 30 in HSF1 wild type cells is confident. Values from duplicate experiments were averaged, and the average fold changes were calculated. Keywords = yeast Keywords = HSF1 Keywords: other
Project description:Heat shock factor 1 (HSF1) is a key regulator of transcriptional responses to proteotoxic stress. It has been recently linked to signaling of estrogen via ESR1. To study the cooperation of HSF1 and ESR1 in the transcriptional response to estrogen, we established estrogen receptor (ER)-positive breast cancer cell lines with reduced HSF1 levels using specific shRNA or CRISPR/Cas9 approach. HSF1 deficiency led to the inhibition of the mitogenic effect of estrogen in MCF7 and T47D cells. RNA-seq analyses revealed that the stimulatory effect of E2 on the transcriptome was smaller in HSF1-deficient MCF7 cells. This could partially result from the higher basal expression of E2-dependent genes in these cells as a consequence of the enhanced binding of unliganded ESR1 to chromatin, which was revealed by ChIP-seq analyses. Thus, we postulate that some fraction of ESR1 could be released from the inhibitory complex with HSP90 and gain transcriptional competence without E2-stimulation.
Project description:Host protein folding stress responses can play important roles in RNA virus replication and evolution. Intriguingly, prior work revealed a complicated interplay between the cytosolic proteostasis stress response, controlled by its master regulator heat shock factor 1 (HSF1) and human immunodeficiency virus-1 (HIV-1). We sought to isolate HSF1 transcription factor activity from proteostasis stress and elucidate the function of HSF1 in HIV-1 lifecycle in absence of cellular stress. We used chemical genetic, stress-independent control of HSF1 activity to establish whether and how HSF1 influences HIV-1 replication. Stress-independent HSF1 induction decreased both the total quantity and infectivity of HIV-1 virions. Moreover, HIV-1 was unable to escape HSF1-mediated restriction over the course of several serial passages. These results promote continued consideration of the heat shock response as a potential target for antiviral drugs.
Project description:To examine whether HSF1-PARP1-PARP13 complex regulates the expression of genes, we performed DNA microarray analysis. We also performed DNA microarray analysis to identify doxorubicin-induced genes,.
Project description:Interventions: experimental group :PD-1 Knockout Engineered T Cells
Primary outcome(s): Number of participants with Adverse Events and/or Dose Limiting Toxicities as a Measure of Safety and tolerability of dose of PD-1 Knockout T cells using Common Terminology Criteria for Adverse Events (CTCAE v4.0) in patients
Study Design: historical control