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dc.contributor.authorAdler, Amos
dc.contributor.authorPark, Yoon-Dong
dc.contributor.authorLarsen, Peter
dc.contributor.authorNagarajan, Vijayaraj
dc.contributor.authorWollenberg, Kurt
dc.contributor.authorQiu, Jin
dc.contributor.authorMyers, Timothy G.
dc.contributor.authorWilliamson, Peter R.
dc.date.accessioned2012-08-16T18:36:47Z
dc.date.available2012-08-16T18:36:47Z
dc.date.issued2011-06
dc.identifier.bibliographicCitationAdler, A., Park, Y. D., Larsen, P., Nagarajan, V., Wollenberg, K., Qiu, J., Myers, T. G., & Williamson, P. R. 2011. A Novel Specificity Protein 1 (SP1)-like Gene Regulating Protein Kinase C-1 (Pkc1)-dependent Cell Wall Integrity and Virulence Factors in Cryptococcus neoformans. Journal of Biological Chemistry, 286(23): 20977-20990. doi: 10.1074/jbc.M111.230268en
dc.identifier.issn0021-9258
dc.identifier.otherdoi: 10.1074/jbc.M111.230268
dc.identifier.urihttp://hdl.handle.net/10027/8497
dc.descriptionThis research was originally published in Journal of Biological Chemistry. Amos Adler, Yoon-Dong Park, Peter Larsen, Vijayaraj Nagarajan5, Kurt Wollenberg, Jin Qiu, Timothy G. Myers and Peter R. Williamson. A Novel Specificity Protein 1 (SP1)-like Gene Regulating Protein Kinase C-1 (Pkc1)-dependent Cell Wall Integrity and Virulence Factors in Cryptococcus neoformans. Journal of Biological Chemistry. 2011. 286:20977-20990. © the American Society for Biochemistry and Molecular Biology doi: 10.1074/jbc.M111.230268en
dc.description.abstractEukaryotic cells utilize complex signaling systems to detect their environments, responding and adapting as new conditions arise during evolution. The basidiomycete fungus Cryptococcus neoformans is a leading cause of AIDS-related death worldwide and utilizes the calcineurin and protein kinase C-1 (Pkc1) signaling pathways for host adaptation and expression of virulence. In the present studies, a C-terminal zinc finger transcription factor, homologous to both the calcineurin responsive zinc fingers (Crz1) of ascomycetes and to the Pkc1 dependent specificity protein-1 (Sp1) transcription factors of metazoans, was identified and named SP1 because of its greater similarity to the metazoan factors. Structurally, the Cn Sp1 protein was found to have acquired an additional Zn finger motif from that of Crz1 and showed Pkc1 dependent phosphorylation, nuclear localization and whole genome epistatic associations under starvation conditions. Transcriptional targets of Cn Sp1 shared functional similarities with Crz1 factors such as cell wall synthesis, but gained the regulation of processes involved in carbohydrate metabolism including trehalose metabolism and lost others such as the induction of autophagy. In addition, overexpression of Cn Sp1 in a pkc1Δ mutant showed restoration of altered phenotypes involved in virulence including cell wall stability, nitrosative stress and extracellular capsule production. Cn Sp1 was also found to be important for virulence of the fungus using a mouse model. In summary, these data suggest an evolutionary shift in C-terminal Zn finger proteins during fungal evolution, transforming them from calcineurin-dependent to PKC1- dependent transcription factors, helping to shape the role of fungal pathogenesis of Cryptococcus neoformans.en
dc.description.sponsorshipThis work was supported, in part, by United States Public Health Service Grant NIH-AI45995, AI49371. This research was also supported, in part, by the Intramural Research Program of the NIH, NIAID.en
dc.language.isoen_USen
dc.publisherAmerican Society for Biochemistry and Molecular Biologyen
dc.titleA Novel Specificity Protein 1 (SP1)-like Gene Regulating Protein Kinase C-1 (Pkc1)-dependent Cell Wall Integrity and Virulence Factors in Cryptococcus neoformansen
dc.typeArticleen


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