The Fungal Cell Death Regulator czt-1 Is Allelic to acr-3
Abstract
Fungal infections have far-reaching implications that range from severe human disease to a panoply of disruptive agricultural and ecological effects, making it imperative to identify and understand the molecular pathways governing the response to antifungal compounds. In this context, CZT-1 (cell death-activated zinc cluster transcription factor) functions as a master regulator of cell death and drug susceptibility in Neurospora crassa. Here we provide evidence indicating that czt-1 is allelic to acr-3, a previously described locus that we now found to harbor a point mutation in its coding sequence. This nonsynonymous amino acid substitution in a low complexity region of CZT-1/ACR-3 caused a robust gain-of-function that led to reduced sensitivity to acriflavine and staurosporine, and increased expression of the drug efflux pump abc-3. Thus, accumulating evidence shows that CZT-1 is an important broad regulator of the cellular response to various antifungal compounds that appear to share common molecular targets.
- Authors:
-
[1];
[1]
- University of Porto (Portugal)
- Kansas State University, Manhattan, KS (United States)
- University of California, Berkeley, CA (United States); Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
- Publication Date:
- Research Org.:
- Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
- Sponsoring Org.:
- USDOE; FCT Portugal; FEDER; National Science Foundation (NSF)
- OSTI Identifier:
- 1628395
- Grant/Contract Number:
- AC02-05CH11231; PEst-C/SAU/LA0002/2013; FCOMP-01-0124-FEDER-037277; NORTE-07-0124-FEDER-000003; DBI 0742713
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Journal of Fungi
- Additional Journal Information:
- Journal Volume: 5; Journal Issue: 4; Journal ID: ISSN 2309-608X
- Publisher:
- MDPI
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; antimicrobial drug resistance; cell death; CZT-1; ABC-3; acriflavine; staurosporine
Citation Formats
Gonçalves, A. Pedro, McCluskey, Kevin, Glass, N. Louise, and Videira, Arnaldo. The Fungal Cell Death Regulator czt-1 Is Allelic to acr-3. United States: N. p., 2019.
Web. doi:10.3390/jof5040114.
Gonçalves, A. Pedro, McCluskey, Kevin, Glass, N. Louise, & Videira, Arnaldo. The Fungal Cell Death Regulator czt-1 Is Allelic to acr-3. United States. https://doi.org/10.3390/jof5040114
Gonçalves, A. Pedro, McCluskey, Kevin, Glass, N. Louise, and Videira, Arnaldo. Sun .
"The Fungal Cell Death Regulator czt-1 Is Allelic to acr-3". United States. https://doi.org/10.3390/jof5040114. https://www.osti.gov/servlets/purl/1628395.
@article{osti_1628395,
title = {The Fungal Cell Death Regulator czt-1 Is Allelic to acr-3},
author = {Gonçalves, A. Pedro and McCluskey, Kevin and Glass, N. Louise and Videira, Arnaldo},
abstractNote = {Fungal infections have far-reaching implications that range from severe human disease to a panoply of disruptive agricultural and ecological effects, making it imperative to identify and understand the molecular pathways governing the response to antifungal compounds. In this context, CZT-1 (cell death-activated zinc cluster transcription factor) functions as a master regulator of cell death and drug susceptibility in Neurospora crassa. Here we provide evidence indicating that czt-1 is allelic to acr-3, a previously described locus that we now found to harbor a point mutation in its coding sequence. This nonsynonymous amino acid substitution in a low complexity region of CZT-1/ACR-3 caused a robust gain-of-function that led to reduced sensitivity to acriflavine and staurosporine, and increased expression of the drug efflux pump abc-3. Thus, accumulating evidence shows that CZT-1 is an important broad regulator of the cellular response to various antifungal compounds that appear to share common molecular targets.},
doi = {10.3390/jof5040114},
journal = {Journal of Fungi},
number = 4,
volume = 5,
place = {United States},
year = {2019},
month = {12}
}
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