Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, São Paulo, Brazil.
Mol Microbiol. 2010 Dec;78(5):1259-79. doi: 10.1111/j.1365-2958.2010.07403.x. Epub 2010 Oct 14.
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.
先前，我们证实了构巢曲霉中蛋白激酶 C pkcA 的 calC2 突变能够赋予其对法尼醇（FOH）的耐受性，FOH 是一种已被证明能够抑制增殖并诱导细胞凋亡的异戊二烯。在这里，我们更详细地研究了 A. nidulans pkcA 在 FOH 耐受性中的作用。我们证明了在 FOH 暴露期间过表达 pkcA 会导致细胞死亡增加。FOH 还能够激活内质网（ER）应激和未折叠蛋白反应（UPR）的几个标志物。我们的结果表明，在 FOH 诱导的细胞死亡过程中，PkcA 和 UPR 之间存在强烈的串扰。此外，pkcA 的过表达增加了 mRNA 积累和 metacaspases 的活性，并且 PkcA 和半胱氨酸蛋白酶样蛋白 CasA 之间存在遗传相互作用。突变分析表明，MAP 激酶参与了对 FOH 作用引起的信号转导。
