Unique integrated stress response sensors regulate cancer cell susceptibility when Hsp70 activity is compromised
- University of Pittsburgh, United States
- Women's Cancer Research Center, UPMC Hillman Cancer Center, Magee-Women Research Institute, United States
- Institute for Precision Medicine, United States
Abstract
AMPK, AMP-activated protein Kinase; AKT, AK strain Transforming serine/threonine kinase; ASNS, asparagine synthetase; ATF4, activating transcription factor 4; ATF6, activating transcription factor 6; BiP, Immunoglobulin Binding Protein; CHOP, C/EBP homologous protein; CQ, chloroquine; DTT, 1,4-Dithiothreitol; EBSS, Earle's balanced salt solution; eIF2α, eukaryotic initiation factor 2 alpha; ER, endoplasmic reticulum; ERAD, endoplasmic reticulum associated degradation; FBS, fetal bovine serum; GCN2, general control non-derepressible 2 factor; GFP, green fluorescent protein; HER2, epidermal growth factor receptor 2; HIF1α, Hypoxia Inducible Factor 1 Subunit Alpha; HRI, heme-regulated inhibitor kinase; Hsp70, heat shock protein 70; IRE1, inositol-required enzyme 1; ISR, integrated stress response; MAL3-101, phenylmethyl 4-[1,1'-biphenyl]-4-yl-1-[6-[[2-(butylamino)-1-[3-(methoxycarbonyl)-4-(2-methoxy-2-oxoethoxy)phenyl]-2-oxoethyl]hexylamino]-6-oxohexyl]-1,2,3,4-tetrahydro-6-methyl-2-oxo-5-pyrimidinecarboxylate; mTOR, mechanistic Target Of Rapamycin; PBS, phosphate buffered saline; PERK, PKR-like endoplasmic reticulum resident kinase; PI, propidium iodide; PKR, Protein Kinase RNA-activated; RFP, red fluorescent protein; RPPA, Reverse Phase Protein Array; S6K, 70‐kDa ribosomal protein S6 kinase; TNBC, triple negative breast cancer; UPR, unfolded protein response; XbpI, X-box binding protein 1.
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All data generated or analysed during this study are included in the manuscript and source files.
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Author details
Funding
European Molecular Biology Laboratory (post-doctoral fellowship (ALTF 823-2016))
- Sara Sannino
National Institutes of Health (F30CA250167)
- Megan E Yates
National Institutes of Health (GM131732)
- Jeffrey L Brodsky
National Institutes of Health (DK79307)
- Jeffrey L Brodsky
National Institutes of Health (P30CA047904)
- Jeffrey L Brodsky
Howard Hughes Medical Institute (Howard Hughes Medical Institute Collaborative Innovation award)
- Jeffrey L Brodsky
University of Pittsburgh (Translational and Precision Pharmacology programs (pilot grant))
- Jeffrey L Brodsky
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2021, Sannino et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Unique integrated stress response sensors regulate cancer cell susceptibility when Hsp70 activity is compromised
eLife 10:e64977.
https://doi.org/10.7554/eLife.64977
