Candida glabrata PHO4 Is Necessary and Sufficient for Pho2-Independent Transcription of Phosphate Starvation Genes
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Comparative genomic analyses of Candida glabrata and Saccharomyces cerevisiae suggest many signal transduction pathways are highly conserved. Focusing on the phosphate signal transduction (PHO) pathway of C. glabrata, we demonstrate that components of the pathway are conserved and confirm the role of CgPHO81, CgPHO80, CgPHO4, and CgMSN5 in the PHO pathway through deletion analysis. Unlike S. cerevisiae, C. glabrata shows little dependence on the transcription factor, Pho2, for induction of phosphate-regulated genes during phosphate limitation. We show that the CgPho4 protein is necessary and sufficient for Pho2-independent gene expression; CgPho4 is capable of driving expression of PHO promoters in S. cerevisiae in the absence of ScPHO2. On the basis of the sequences of PHO4 in the hemiascomycetes and complementation analysis, we suggest that Pho2 dependence is a trait only observed in species closely related to S. cerevisiae. Our data are consistent with trans-regulatory changes in the PHO pathway via the transcription factor Pho4 as opposed to cis-regulatory changes (the promoter).
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The PHO pathway executes the phosphate starvation response in C. glabrata via the transcription factor CgPho4, which is regulated by the CgPho80/CgPho85/CgPho81 complex.
“The PHO (phosphate signal transduction) pathway executes the phosphate starvation response in C. glabrata via the transcription factor CgPho4, which itself is regulated by the cyclin (CgPho80)/cyclin-dependent protein kinase (CDK; CgPho85)/CDK inhibitor (CgPho81) complex [115].”
From Candida glabrata: A Lot More Than Meets the Eye (2019) · cites this paper as [115]
CgPMU2 and CgPHO gene expression is regulated by CgPho4 in a largely CgPho2 coactivator-independent manner.
“Furthermore, CgPMU2 and CgPHO gene expression was found to be regulated by CgPho4 in a largely CgPho2 coactivator-independent manner [115,117].”
From Candida glabrata: A Lot More Than Meets the Eye (2019) · cites this paper as [115]
CgPho4 is required for phosphate starvation-induced phosphatase activity.
“CgPho4 was found to be required for the phosphate starvation-induced phosphatase activity, and deletion of the putative CgPho4 nuclear exporter, CgMsn5, led to increased phosphatase activity under phosphate-surplus conditions [115].”
From Candida glabrata: A Lot More Than Meets the Eye (2019) · cites this paper as [115]
The C. glabrata genome lacks an ortholog of the S. cerevisiae PHO5 gene, which codes for a phosphate starvation-inducible acid phosphatase.
“However, the C. glabrata genome lacks an ortholog of the S. cerevisiae PHO5 gene which codes for a phosphate starvation-inducible acid phosphatase [115].”
From Candida glabrata: A Lot More Than Meets the Eye (2019) · cites this paper as [115]
Deletion of the putative CgPho4 nuclear exporter CgMsn5 led to increased phosphatase activity under phosphate-surplus conditions.
“CgPho4 was found to be required for the phosphate starvation-induced phosphatase activity, and deletion of the putative CgPho4 nuclear exporter, CgMsn5, led to increased phosphatase activity under phosphate-surplus conditions [115].”
From Candida glabrata: A Lot More Than Meets the Eye (2019) · cites this paper as [115]
Cites
Sikorski, R. S., & Hieter, P. (1989) · Genetics · doi:10.1093/genetics/122.1.19 · Cited by 8,685 · see citing works
Longtine, M. S., Mckenzie, A., DeMarini, D. J., Shah, N. G., Wach, A., Brachat, A., Philippsen, P., & Pringle, J. R. (1998) · Yeast · doi:10.1002/(sici)1097-0061(199807)14:10 · Cited by 5,367 · see citing works
King, M.-C., & Wilson, A. C. (1975) · Science · doi:10.1126/science.1090005 · Cited by 2,815 · see citing works
Dujon, B., Sherman, D., Fischer, G., Durrens, P., Casaregola, S., Lafontaine, I., de Montigny, J., Marck, C., Neuvéglise, C., Talla, E., et al. (2004) · Nature · doi:10.1038/nature02579 · Cited by 1,623 · see citing works
Robustness in bacterial chemotaxis
Alon, U. S., Surette, M. G., Barkai, N., & Leibler, S. (1999) · Nature · doi:10.1038/16483 · Cited by 1,129 · see citing works
Evolutionary changes in cis and trans gene regulation
Wittkopp, P. J., Haerum, B. K., & Clark, A. G. (2004) · Nature · doi:10.1038/nature02698 · Cited by 873 · see citing works
Finding Functional Features in Saccharomyces Genomes by Phylogenetic Footprinting
Cliften, P. F., Sudarsanam, P., Desikan, A., Fulton, L. A., Fulton, B., Majors, J. E., Waterston, R., Cohen, B. A., & Johnston, M. (2003) · Science · doi:10.1126/science.1084337 · Cited by 805 · see citing works
Yesterday's polyploids and the mystery of diploidization
Wolfe, K. H. (2001) · Nature Reviews Genetics · doi:10.1038/35072009 · Cited by 767 · see citing works
Byrne, K. P., & Wolfe, K. H. (2005) · Genome Research · doi:10.1101/gr.3672305 · Cited by 720 · see citing works
A Single Amino Acid Mutation Contributes to Adaptive Beach Mouse Color Pattern
Hoekstra, H. E., Hirschmann, R. J., Bundey, R. A., Insel, P. A., & Crossland, J. P. (2006) · Science · doi:10.1126/science.1126121 · Cited by 716 · see citing works
Garofalo, C., & Surmacz, E. (2005) · Journal of Cellular Physiology · doi:10.1002/jcp.20472 · Cited by 591 · see citing works
Yeger‐Lotem, E., Sattath, S., Kashtan, N., Itzkovitz, S., Milo, R., Pinter, R. Y., Alon, U. S., & Margalit, H. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0306752101 · Cited by 536 · see citing works
Cormack, B. P., Ghori, N., & Falkow, S. (1999) · Science · doi:10.1126/science.285.5427.578 · Cited by 383 · see citing works
Regulatory changes underlying expression differences within and between Drosophila species
Wittkopp, P. J., Haerum, B. K., & Clark, A. G. (2008) · Nature Genetics · doi:10.1038/ng.77 · Cited by 367 · see citing works
The receptor Msn5 exports the phosphorylated transcription factor Pho4 out of the nucleus
Kaffman, A., Rank, N. M., O’Neill, E., Huang, L. S., & O’Shea, E. K. (1998) · Nature · doi:10.1038/24898 · Cited by 335 · see citing works
Regulation of PHO4 Nuclear Localization by the PHO80-PHO85 Cyclin-CDK Complex
O’Neill, E., Kaffman, A., Jolly, E. R., & O’Shea, E. K. (1996) · Science · doi:10.1126/science.271.5246.209 · Cited by 330 · see citing works
Roles of Phosphorylation Sites in Regulating Activity of the Transcription Factor Pho4
Komeili, A., & O’Shea, E. K. (1999) · Science · doi:10.1126/science.284.5416.977 · Cited by 326 · see citing works
Rewiring of the Yeast Transcriptional Network Through the Evolution of Motif Usage
Ihmels, J., Bergmann, S., Gerami‐Nejad, M., Yanai, I., McClellan, M., Berman, J. G., & Barkai, N. (2005) · Science · doi:10.1126/science.1113833 · Cited by 295 · see citing works
Signaling phosphate starvation
Lenburg, M. E., & O’Shea, E. K. (1996) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(96)10048-7 · Cited by 295 · see citing works
Hentges, P., Driessche, B. V., Tafforeau, L., Vandenhaute, J., & Carr, A. M. (2005) · Yeast · doi:10.1002/yea.1291 · Cited by 274 · see citing works
Large-Scale Turnover of Functional Transcription Factor Binding Sites in Drosophila
Moses, A. M., Pollard, D. A., Nix, D. A., Iyer, V. N., Li, X., Biggin, M. D., & Eisen, M. B. (2006) · PLoS Computational Biology · doi:10.1371/journal.pcbi.0020130 · Cited by 251 · see citing works
Evolution of a Combinatorial Transcriptional Circuit
Tsong, A. E., Miller, M. G., Raisner, R. M., & Johnson, A. D. (2003) · Cell · doi:10.1016/s0092-8674(03)00885-7 · Cited by 250 · see citing works
Nicotinic Acid Limitation Regulates Silencing of <i>Candida</i> Adhesins During UTI
Domergue, R., Castaño, I., De Las Peñas, A., Zupancic, M., Lockatell, V., Hebel, J. R., Johnson, D., & Cormack, B. P. (2005) · Science · doi:10.1126/science.1108640 · Cited by 249 · see citing works
Phosphate Transport and Sensing in Saccharomyces cerevisiae
Wykoff, D. D., & O’Shea, E. K. (2001) · Genetics · doi:10.1093/genetics/159.4.1491 · Cited by 238 · see citing works
Self-citationEvolution of the MAT locus and its Ho endonuclease in yeast species
Butler, G., Kenny, C. C., Fagan, A., Kurischko, C., Gaillardin, C. M., & Wolfe, K. H. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0304170101 · Cited by 236 · see citing works
Phosphate-Regulated Inactivation of the Kinase PHO80-PHO85 by the CDK Inhibitor PHO81
Schneider, K., Smith, R. L., & O’Shea, E. K. (1994) · Science · doi:10.1126/science.7939631 · Cited by 235 · see citing works
The phosphatase system in Saccharomyces cerevisiae.
Oshima, Y. (1997) · Genes & Genetic Systems · doi:10.1266/ggs.72.323 · Cited by 232 · see citing works
Alignment of metabolic pathways
Pinter, R. Y., Rokhlenko, O., Yeger‐Lotem, E., et al. (2005) · Computer applications in the biosciences · doi:10.1093/bioinformatics/bti554 · Cited by 215 · see citing works
Comparative genomics of the environmental stress response in ascomycete fungi
Gasch, A. P. (2007) · Yeast · doi:10.1002/yea.1512 · Cited by 210 · see citing works
Signaling phosphate starvation
Lenburg, M. E. (1996) · Trends in Biochemical Sciences · doi:10.1016/0968-0004(96)10048-7 · Cited by 210 · see citing works
Cormack, B. P., & Falkow, S. (1999) · Genetics · doi:10.1093/genetics/151.3.979 · Cited by 180 · see citing works
Parallel inactivation of multiple GAL pathway genes and ecological diversification in yeasts
Hittinger, C. T., Rokas, A., & Carroll, S. B. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0404319101 · Cited by 178 · see citing works
Rao, C. V., Kirby, J. R., & Arkin, A. P. (2004) · PLoS Biology · doi:10.1371/journal.pbio.0020049 · Cited by 167 · see citing works
Regulation of phosphate acquisition in Saccharomyces cerevisiae
Persson, B. L., Lagerstedt, J. O., Pratt, J. R., Pattison-Granberg, J., Lundh, K. I., Shokrollahzadeh, S., & Lundh, F. (2003) · Current Genetics · doi:10.1007/s00294-003-0400-9 · Cited by 157 · see citing works
Vogel, K. D., Hörz, W., & Hinnen, A. (1989) · Molecular and Cellular Biology · doi:10.1128/mcb.9.5.2050 · Cited by 154 · see citing works
Positive Feedback Regulates Switching of Phosphate Transporters in S. cerevisiae
Wykoff, D. D., Rizvi, A. H., Raser, J. M., Margolin, B., & O’Shea, E. K. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.07.022 · Cited by 119 · see citing works
Self-citationCarroll, A. S., Bishop, A. C., DeRisi, J. L., Shokat, K. M., & O’Shea, E. K. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.211195798 · Cited by 119 · see citing works
Yoshida, K., Ogawa, N., & Oshima, Y. (1989) · Molecular and General Genetics MGG · doi:10.1007/bf00330940 · Cited by 114 · see citing works
Wykoff, D. D., & O’Shea, E. K. (2005) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m400166-mcp200 · Cited by 108 · see citing works
Self-citationPartially Phosphorylated Pho4 Activates Transcription of a Subset of Phosphate-Responsive Genes
Springer, M., Wykoff, D. D., Miller, N. S., et al. (2003) · PLoS Biology · doi:10.1371/journal.pbio.0000028 · Cited by 99 · see citing works
Self-citationTorulopsis glabrata vaginitis: Clinical aspects and susceptibility to antifungal agents
REDONDO-LOPEZ, V., Lynch, M., Schmitt, C., Cook, R. L., & Sobel, J. D. (1991) · International Journal of Gynecology & Obstetrics · doi:10.1016/0020-7292(91)90322-v · Cited by 83 · see citing works
Yoshida, K., Kuromitsu, Z., Ogawa, N., et al. (1989) · Molecular and General Genetics MGG · doi:10.1007/bf00330939 · Cited by 74 · see citing works
Barbarić, S., Münsterkötter, M., Svaren, J. P., & Hörz, W. (1996) · Nucleic Acids Research · doi:10.1093/nar/24.22.4479 · Cited by 74 · see citing works
Huang, S., & O’Shea, E. K. (2005) · Genetics · doi:10.1534/genetics.104.038695 · Cited by 71 · see citing works
Peleg, Y., Addison, R., Aramayo, R., et al. (1996) · Fungal Genetics and Biology · doi:10.1006/fgbi.1996.0034 · Cited by 53 · see citing works
Zhang, F., Kirouac, M., Zhu, N., et al. (1997) · Molecular and Cellular Biology · doi:10.1128/mcb.17.6.3272 · Cited by 50 · see citing works
Differential X Reactivation in Human Placental Cells: Implications for Reversal of X Inactivation
Migeon, B. R., Axelman, J., & Jeppesen, P. (2005) · The American Journal of Human Genetics · doi:10.1086/432815 · Cited by 35 · see citing works
Piano, F., Parisi, M. J., Karess, R. E., & Kambysellis, M. P. (1999) · Genetics · doi:10.1093/genetics/152.2.605 · Cited by 32 · see citing works
Peleg, Y., Aramayo, R., Kang, S., et al. (1996) · Molecular and General Genetics MGG · doi:10.1007/bf02173977 · Cited by 31 · see citing works
Yeast as a model system for anticancer drug discovery
Simon, J. A. (2001) · Emerging Therapeutic Targets · doi:10.1517/14728222.5.2.177 · Cited by 21 · see citing works
The DNA-damage signature in Saccharomyces cerevisiae is associated with single-strand breaks in DNA
Fry, R. C., DeMott, M. S., Cosgrove, J. P., Begley, T. J., Samson, L. D., & Dedon, P. C. (2006) · BMC Genomics · doi:10.1186/1471-2164-7-313 · Cited by 18 · see citing works
Chang, Y.-W., Liu, F.-G. R., Yu, N., Sung, H.-M., Yang, P., Wang, D., Huang, C.-J., Shih, M., & Li, W. (2008) · Molecular Biology and Evolution · doi:10.1093/molbev/msn138 · Cited by 15 · see citing works
Yang, J., Dhamija, S. S., & Schweingruber, M. E. (1991) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1991.tb16041.x · Cited by 12 · see citing works
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Gabaldón, T., Martin, T., Marcet-Houben, M., Durrens, P., Bolotin-Fukuhara, M., Lespinet, O., Arnaise, S., Boisnard, S., Aguileta, G., Atanasova, R., et al. (2013) · BMC Genomics · doi:10.1186/1471-2164-14-623 · Cited by 198 · see citing works
Candida glabrata: A Lot More Than Meets the Eye
Kumar, K., Askari, F., Sahu, M. S., & Kaur, R. (2019) · Microorganisms · doi:10.3390/microorganisms7020039 · Cited by 128 · see citing works
He, B. Z., Zhou, X., & O’Shea, E. K. (2017) · eLife · doi:10.7554/elife.25157 · Cited by 27 · see citing works
Corrigan, M. W., Kerwin-Iosue, C. L., Kuczmarski, A. S., Amin, K. B., & Wykoff, D. D. (2013) · PLoS ONE · doi:10.1371/journal.pone.0069628 · Cited by 23 · see citing works
Orkwis, B. R., Davies, D. L., Kerwin, C. L., Sanglard, D., & Wykoff, D. D. (2010) · Genetics · doi:10.1534/genetics.110.120824 · Cited by 21 · see citing works
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Kerwin, C. L., & Wykoff, D. D. (2012) · FEMS Yeast Research · doi:10.1111/1567-1364.12000 · Cited by 9 · see citing works
Self-citationNahas, J. V., Iosue, C. L., Shaik, N. F., Selhorst, K., He, B. Z., & Wykoff, D. D. (2018) · G3 Genes Genomes Genetics · doi:10.1534/g3.118.200303 · Cited by 8 · see citing works
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- Authors
- Kerwin, C. L., & Wykoff, D. D.
- Affiliations
- Villanova University (US)
- ORCID
- Wykoff, Dennis D
- Venue
- Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-06-01
- Volume
- 182
- Issue
- 2
- Pages
- 471-479
- ISSN
- 0016-6731 (ISSN-L)
- 1943-2631
- PMC
- PMC2691756
- OpenAlex
- W2145967173
- Cited by
- 34
- References
- 53
- Citations by year
- 2026: 4 · 2025: 1 · 2023: 3 · 2022: 1 · 2021: 1 · 2020: 1 · 2019: 1 · 2018: 2 · 2017: 2 · 2016: 2 · 2015: 2 · 2014: 4 · 2013: 3 · 2012: 2
- FWCI
- 0.94
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Genetics (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation (0747799)
- Villanova University
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant nutrient uptake and metabolism
- Keywords
- Candida glabrata, Pho4, PHO2, phosphate limitation, transcriptional regulation, Saccharomyces cerevisiae, gene complementation, hemiascomycetes
- MeSH terms
- Fungal Proteins, Genes, Fungal, Phosphates, Saccharomyces cerevisiae, Transcription, Genetic, Signal Transduction, Genomics, Candida glabrata
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