Evaluation of the Role of Human DNAJAs in the Response to Cytotoxic Chemotherapeutic Agents in a Yeast Model System

BioMed Research International
Aurellia WhitmoreHernan Flores-Rozas

Abstract

Heat-shock proteins (HSPs) play a crucial role in maintaining protein stability for cell survival during stress-induced insults. Overexpression of HSPs in cancer cells results in antiapoptotic activity contributing to cancer cell survival and restricting the efficacy of cytotoxic chemotherapy, which continues to play an important role in the treatment of many cancers, including triple-negative breast cancer (TNBC). First-line therapy for TNBC includes anthracycline antibiotics, which are associated with serious dose-dependent side effects and the development of resistance. We previously identified YDJ1, which encodes a heat-shock protein 40 (HSP40), as an important factor in the cellular response to anthracyclines in yeast, with mutants displaying over 100-fold increased sensitivity to doxorubicin. In humans, the DNAJA HSP40s are homologues of YDJ1. To determine the role of DNAJAs in the cellular response to cytotoxic drugs, we investigated their ability to rescue ydj1Δ mutants from exposure to chemotherapeutic agents. Our results indicate that DNAJA1 and DNAJA2 provide effective protection, while DNAJA3 and DNAJA4 did not. The level of complementation was also dependent on the agent used, with DNAJA1 and DNAJA2 rescuing the yd...Continue Reading

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Methods Mentioned

BETA
protein folding

Software Mentioned

COBALT
MCLAB
GraphPad Prism

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