Involvement of the Aspergillus nidulans protein kinase C with farnesol tolerance is related to the unfolded protein response

Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, São Paulo, Brazil.
Molecular Microbiology (Impact Factor: 5.03). 12/2010; 78(5):1259-79. DOI: 10.1111/j.1365-2958.2010.07403.x
Source: PubMed

ABSTRACT Previously, we demonstrated that the Aspergillus nidulans calC2 mutation in protein kinase C pkcA was able to confer tolerance to farnesol (FOH), an isoprenoid that has been shown to inhibit proliferation and induce apoptosis. Here, we investigate in more detail the role played by A. nidulans pkcA in FOH tolerance. We demonstrate that pkcA overexpression during FOH exposure causes increased cell death. FOH is also able to activate several markers of endoplasmic reticulum (ER) stress and the unfolded protein response (UPR). Our results suggest an intense cross-talk between PkcA and the UPR during FOH-induced cell death. Furthermore, the overexpression of pkcA increases both mRNA accumulation and metacaspases activity, and there is a genetic interaction between PkcA and the caspase-like protein CasA. Mutant analyses imply that MAP kinases are involved in the signal transduction in response to the effects caused by FOH.

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Available from: Gustavo Goldman, Jul 10, 2015
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    • "Two proteins have been identified in this response; the Gα subunit FadA of a heterotrimeric G protein, where hyperactivation leads to a strong increase in farnesol sensitivity [38], and the kinase PkcA. Mutation of PkcA increases resistance to farnesol while overexpression results in a higher rate of cell death in response to the QSM [41]. Finally, farnesol has also been described to induce apoptosis of cancerous cells in vivo (see review [42]), as well as increasing antibiotic sensitivity of Staphylococcus aureus [43]. "
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