The Fungal Cell Death Regulator czt-1 Is Allelic to acr-3

Gonçalves, A. Pedro; McCluskey, Kevin; Glass, N. Louise; Videira, Arnaldo

doi:10.3390/jof5040114

Title: The Fungal Cell Death Regulator czt-1 Is Allelic to acr-3

Journal Article · 01 December 2019 · Journal of Fungi

DOI: https://doi.org/10.3390/jof5040114 · OSTI ID:1628395

^[1]; McCluskey, Kevin ^[2]; Glass, N. Louise ^[3];

^[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)

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.

View Accepted Manuscript (DOE)

Cite

Export

Save

Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE; FCT Portugal; FEDER; National Science Foundation (NSF)

Grant/Contract Number:: AC02-05CH11231; PEst-C/SAU/LA0002/2013; FCOMP-01-0124-FEDER-037277; NORTE-07-0124-FEDER-000003; DBI 0742713

OSTI ID:: 1628395

Journal Information:: Journal of Fungi, Vol. 5, Issue 4; ISSN 2309-608X

Publisher:: MDPICopyright Statement

Country of Publication:: United States

Language:: English

References (25)

Rediscovery by Whole Genome Sequencing: Classical Mutations and Genome Polymorphisms in Neurospora crassa McCluskey, Kevin; Wiest, Aric E.; Grigoriev, Igor V. G3: Genes\|Genomes\|Genetics, Vol. 1, Issue 4 https://doi.org/10.1534/g3.111.000307	journal	September 2011
The fungal threat to global food security Avery, Simon V.; Singleton, Ian; Magan, Naresh Fungal Biology, Vol. 123, Issue 8 https://doi.org/10.1016/j.funbio.2019.03.006	journal	August 2019
Acriflavin resistance controlled by chromosomal genes in Neurospora Hsu, K. S. Fungal Genetics Reports, Vol. 8, Issue 1 https://doi.org/10.4148/1941-4765.2082	journal	December 1965
Molecular and phenotypic characterization of yeast PDR1 mutants that show hyperactive transcription of various ABC multidrug transporter genes Carvajal, E.; van den Hazel, H. B.; Cybularz-Kolaczkowska, A. Molecular and General Genetics MGG, Vol. 256, Issue 4 https://doi.org/10.1007/s004380050584	journal	October 1997
A quantitative analysis of kinase inhibitor selectivity Karaman, Mazen W.; Herrgard, Sanna; Treiber, Daniel K. Nature Biotechnology, Vol. 26, Issue 1 https://doi.org/10.1038/nbt1358	journal	January 2008
Proflavine/acriflavine derivatives with versatile biological activities Sabolova, Danica; Kristian, Pavol; Kozurkova, Mária Journal of Applied Toxicology, Vol. 40, Issue 1 https://doi.org/10.1002/jat.3818	journal	June 2019
Modulation of fungal sensitivity to staurosporine by targeting proteins identified by transcriptional profiling Fernandes, Andreia S.; Pedro Gonçalves, A.; Castro, Ana Fungal Genetics and Biology, Vol. 48, Issue 12 https://doi.org/10.1016/j.fgb.2011.09.004	journal	December 2011
Food security in 2044: How do we control the fungal threat? Kettles, Graeme J.; Luna, Estrella Fungal Biology, Vol. 123, Issue 8 https://doi.org/10.1016/j.funbio.2019.04.006	journal	August 2019
A Putative Zn2Cys6 Transcription Factor Is Associated With Isoprothiolane Resistance in Magnaporthe oryzae Wang, Zuo-Qian; Meng, Fan-Zhu; Zhang, Ming-Ming Frontiers in Microbiology, Vol. 9 https://doi.org/10.3389/fmicb.2018.02608	journal	October 2018
DNA-PKcs, a novel functional target of acriflavine, mediates acriflavine's p53-dependent synergistic anti-tumor efficiency with melphalan Cao, Ji; Lin, Guanyu; Gong, Yanling Cancer Letters, Vol. 383, Issue 1 https://doi.org/10.1016/j.canlet.2016.09.029	journal	December 2016
Molecular cloning of the acr-2 gene which controls acriflavine sensitivity in Neurospora crassa Akiyama, Masashi; Nakashima, Hideaki Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression, Vol. 1307, Issue 2 https://doi.org/10.1016/0167-4781(96)00042-5	journal	June 1996
Gain of Function Mutations in CgPDR1 of Candida glabrata Not Only Mediate Antifungal Resistance but Also Enhance Virulence Ferrari, Sélène; Ischer, Françoise; Calabrese, David PLoS Pathogens, Vol. 5, Issue 1 https://doi.org/10.1371/journal.ppat.1000268	journal	January 2009
Coping with Stress and the Emergence of Multidrug Resistance in Fungi Shor, Erika; Perlin, David S. PLOS Pathogens, Vol. 11, Issue 3 https://doi.org/10.1371/journal.ppat.1004668	journal	March 2015
Involvement of mitochondrial proteins in calcium signaling and cell death induced by staurosporine in Neurospora crassa Gonçalves, A. Pedro; Cordeiro, J. Miguel; Monteiro, João Biochimica et Biophysica Acta (BBA) - Bioenergetics, Vol. 1847, Issue 10 https://doi.org/10.1016/j.bbabio.2015.05.011	journal	October 2015
DNA sequencing with chain-terminating inhibitors Sanger, F.; Nicklen, S.; Coulson, A. R. Proceedings of the National Academy of Sciences, Vol. 74, Issue 12 https://doi.org/10.1073/pnas.74.12.5463	journal	December 1977
The global problem of antifungal resistance: prevalence, mechanisms, and management Perlin, David S.; Rautemaa-Richardson, Riina; Alastruey-Izquierdo, Ana The Lancet Infectious Diseases, Vol. 17, Issue 12 https://doi.org/10.1016/S1473-3099(17)30316-X	journal	December 2017
Analysis of the DNA sequence of the putative ABC transporter NCU09975 in Neurospora crassa strains carrying acriflavin resistance markers. Wiest, Aric E.; Koch, Sarah; McCluskey, Kevin Fungal Genetics Reports, Vol. 59, Issue 1 https://doi.org/10.4148/1941-4765.1012	journal	January 2012
CZT-1 Is a Novel Transcription Factor Controlling Cell Death and Natural Drug Resistance in Neurospora crassa Gonçalves, A. Pedro; Hall, Charles; Kowbel, David J. G3: Genes\|Genomes\|Genetics, Vol. 4, Issue 6 https://doi.org/10.1534/g3.114.011312	journal	April 2014
New markers and map sequences inNeurospora crassa, with a description of mapping by duplication coverage, and of multiple translocation stocks for testing linkage Perkins, David D.; Newmeyer, Dorothy; Taylor, Cecile W. Genetica, Vol. 40, Issue 1 https://doi.org/10.1007/BF01787357	journal	December 1969
Functional Profiling of Transcription Factor Genes in Neurospora crassa Carrillo, Alexander J.; Schacht, Patrick; Cabrera, Ilva E. G3: Genes\|Genomes\|Genetics, Vol. 7, Issue 9 https://doi.org/10.1534/g3.117.043331	journal	July 2017
The Global Burden of Fungal Diseases Vallabhaneni, Snigdha; Mody, Rajal K.; Walker, Tiffany Infectious Disease Clinics of North America, Vol. 30, Issue 1 https://doi.org/10.1016/j.idc.2015.10.004	journal	March 2016
Regulated Forms of Cell Death in Fungi Gonçalves, A. Pedro; Heller, Jens; Daskalov, Asen Frontiers in Microbiology, Vol. 8 https://doi.org/10.3389/fmicb.2017.01837	journal	September 2017
The Fungal Genetics Stock Center: a repository for 50 years of fungal genetics research McCluskey, K.; Wiest, A.; Plamann, M. Journal of Biosciences, Vol. 35, Issue 1 https://doi.org/10.1007/s12038-010-0014-6	journal	January 2010
Activation of a TRP-like channel and intracellular Ca2+ dynamics during phospholipase-C-mediated cell death Goncalves, A. P.; Cordeiro, J. M.; Monteiro, J. Journal of Cell Science, Vol. 127, Issue 17 https://doi.org/10.1242/jcs.152058	journal	July 2014
Aminoacridines, potent inhibitors of protein kinase C. Hannun, Y. A.; Bell, R. M. Journal of Biological Chemistry, Vol. 263, Issue 11 https://doi.org/10.1016/S0021-9258(18)60688-X	journal	April 1988

Similar Records

Programmed Cell Death in Neurospora crassa Is Controlled by the Allorecognition Determinant rcd-1

Journal Article · 2019 · Genetics · OSTI ID:1591842

Daskalov, Asen; Gladieux, Pierre; Heller, Jens; +1 more

Human-Like Eukaryotic Translation Initiation Factor 3 from Neurospora crassa

Journal Article · 2013 · PLoS ONE · OSTI ID:1627650

Smith, M. Duane; Gu, Yu; Querol-Audí, Jordi; +3 more

D-Tailor: automated analysis and design of DNA sequences

Journal Article · 2014 · Bioinformatics · OSTI ID:1625285

Guimaraes, Joao C.; Rocha, Miguel; Arkin, Adam P.; +1 more

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
antimicrobial drug resistance
cell death
CZT-1
ABC-3
acriflavine
staurosporine

Title: The Fungal Cell Death Regulator czt-1 Is Allelic to acr-3

Citation Formats

References (25)

Similar Records

Related Subjects