Regulatory mechanism of the atypical AP-1-like transcription factor yap1 in Cryptococcus neoformans

Yee Seul So, Shinae Maeng, Dong Hoon Yang, Hyelim Kim, Kyung Tae Lee, Seong Ryong Yu, Jennifer L. Tenor, Vinay K. Giri, Dena L. Toffaletti, Samantha Arras, James A. Fraser, John R. Perfect, Yong Sun Bahn

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

AP-1-like transcription factors play evolutionarily conserved roles as redox sensors in eukaryotic oxidative stress responses. In this study, we aimed to elucidate the regulatory mechanism of an atypical yeast AP-1-like protein, Yap1, in the stress response and virulence of Cryptococcus neoformans. YAP1 expression was induced and involved not only by oxidative stresses, such as H2O2 and diamide, but also by other environmental stresses, such as osmotic and membrane-destabilizing stresses. Yap1 was distributed throughout both the cytoplasm and the nucleus under basal conditions and more enriched within the nucleus in response to diamide but not to other stresses. Deletion of the C-terminal cysteine-rich domain (c-CRD),where the nuclear export signal resides, increased nuclear enrichment of Yap1 under basal conditions and altered resistance to oxidative stresses but did not affect the role of Yap1 in other stress responses and cellular functions. As a potential upstream regulator of Yap1, we discovered that Mpk1 is positively involved, but Hog1 is mostly dispensable. Pleiotropic roles forYap1 in diverse biological processes were supported by transcriptome data showing that 162 genes are differentially regulated by Yap1, with further analysis revealing that Yap1 promotes cellular resistance to toxic cellular metabolites produced during glycolysis, such as methylglyoxal. Finally,we demonstrated that Yap1 plays a minor role in the survival of C. neoformans within hosts.

Original languageEnglish
Article numbere00785
JournalmSphere
Volume4
Issue number6
DOIs
Publication statusPublished - 2019

Bibliographical note

Funding Information:
The authors declare that no competing interests exist. This work was supported by National Research Foundation (NRF) grants funded by the Korean government (MSIT) (2016R1E1A1A01943365 and 2018R1A5A1025077 to Y.-S.B.; 2018R1C1B6009031 to K.-T.L.) and by the Strategic Initiative for Microbiomes in Agriculture and Food funded by Ministry of Agriculture, Food and Rural Affairs (918012-4 to Y.-S.B.). This work was also supported in part by Public Health Service grants AI73896 and AI93257 (to J.R.P.).

Funding Information:
This work was supported by National Research Foundation (NRF) grants funded by the Korean government (MSIT) (2016R1E1A1A01943365 and 2018R1A5A1025077 to Y.-S.B.; 2018R1C1B6009031 to K.-T.L.) and by the Strategic Initiative for Microbiomes in Agriculture and Food funded by Ministry of Agriculture, Food and Rural Affairs (918012-4 to Y.-S.B.). This work was also supported in part by Public Health Service grants AI73896 and AI93257 (to J.R.P.).

Publisher Copyright:
© 2019 So et al.

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Molecular Biology

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