What is the role of ELAVL1 in gemcitabine resistance, and how does AHR modulation affect its function?

Label:chem

Topic
ELAVL1 (human antigen R) is an RNA-binding protein that stabilizes mRNAs of genes involved in cell proliferation, apoptosis, and chemoresistance. It is crucial for the expression of DCK, the rate-limiting enzyme in gemcitabine activation. AHR has been shown to regulate ELAVL1 localization, potentially contributing to chemoresistance.
Answer
ELAVL1 must be located in the cytoplasm to stabilize DCK mRNA and promote gemcitabine activation. AHR activity can restrict ELAVL1 translocation to the cytoplasm, leading to reduced DCK expression and gemcitabine resistance. Inhibition of AHR with BAY promotes ELAVL1 translocation to the cytoplasm, enhancing DCK expression and improving gemcitabine response. Conversely, AHR activation with tapinarof restricts ELAVL1 translocation, reducing DCK expression and decreasing gemcitabine effectiveness.
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