Article

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.

Download full-text

Full-text

Available from: Gustavo Goldman, Jul 10, 2015
1 Follower
 · 
98 Views
  • Source
    • "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]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: We will discuss fungal communication in the context of fundamental biological functions including mating, growth, morphogenesis, and the regulation of fungal virulence determinants. We will address intraspecies but also interkingdom signaling by systematically discussing the sender of the message, the molecular message, and receiver. Analyzing communication shows the close coevolution of fungi with organisms present in their environment giving insights into multispecies communication. A better understanding of the molecular mechanisms underlying microbial communication will promote our understanding of the "fungal communicome."
    International Journal of Microbiology 01/2012; 2012:351832. DOI:10.1155/2012/351832
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Upon apoptosis induction, translocation of mammalian mitochondrial endonuclease G (EndoG) to the nucleus coincides with large-scale DNA fragmentation. Here, we describe for the first time a homologue of EndoG in filamentous fungi by investigating if the Aspergillus nidulans homologue of the EndoG gene, named nucA(EndoG), is being activated during farnesol-induced cell death. Our results suggest that NucA is not involved in cell death, but it plays a role in the DNA-damaging response in A. nidulans.
    Eukaryotic Cell 02/2011; 10(2):276-83. DOI:10.1128/EC.00224-10 · 3.18 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Metacaspases are cysteine-dependent proteases found in protozoa, fungi and plants and are distantly related to metazoan caspases. Although metacaspases share structural properties with those of caspases, they lack Asp specificity and cleave their targets after Arg or Lys residues. Studies performed over the past 10 years have demonstrated that metacaspases are multifunctional proteases essential for normal physiology of non-metazoan organisms. This article provides a comprehensive overview of the metacaspase function and molecular regulation during programmed cell death, stress and cell proliferation, as well as an analysis of the first metacaspase-mediated proteolytic pathway. To prevent further misapplication of caspase-specific molecular probes for measuring and inhibiting metacaspase activity, we provide a list of probes suitable for metacaspases.
    Cell death and differentiation 05/2011; 18(8):1279-88. DOI:10.1038/cdd.2011.66 · 8.39 Impact Factor
Show more