Open AccessChemogenomic and bioinformatic profiling of ERdj paralogs underpins their unique roles in cancer
Author(s) -
Laura E. Knighton,
. Nitika,
Tasaduq Hussain Wani,
Andrew W. Truman
Publication year - 2022
Publication title -
cell stress and chaperones
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.994
H-Index - 87
eISSN - 1466-1268
pISSN - 1355-8145
DOI - 10.1007/s12192-022-01256-2
Subject(s) - proteostasis , biology , computational biology , cancer , genetics , bioinformatics , cancer research
The ER-resident Hsp70 paralog BiP is important in cellular homeostasis as well as in cancer cell progression. Although several BiP inhibitors have been developed, they have not succeeded in clinical trials due to toxicity issues. ER-resident co-chaperones (ERdjs) tailor the activity and specificity of BiP. Here, we report multiple-cancer analyses of BiP and ERdj genomic alterations including mRNA expression from cancer patients using available data from The Cancer Genome Atlas (TCGA). We examine the individual roles of BiP co-chaperones ERdj1-8 in mediating anticancer drug resistance through chemogenomic screening of ERdj1-8 CRISPR KO cells. In keeping with the idea that ERdjs regulate distinct facets of proteostasis, we find that each ERdj KO displays a unique signature of drug resistance. Taken together, our results demonstrate a novel way to understand functional specificity of ERdjs, suggesting a future personalized medicine approach, whereby ERdj mutation status is assessed to design an effective anticancer treatment plan.