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Unique evolution of the UPR pathway with a novel bZIP transcription factor, Hxl1, for controlling pathogenicity of Cryptococcus neoformans.

Publication ,  Journal Article
Cheon, SA; Jung, K-W; Chen, Y-L; Heitman, J; Bahn, Y-S; Kang, HA
Published in: PLoS Pathog
August 2011

In eukaryotic cells, the unfolded protein response (UPR) pathway plays a crucial role in cellular homeostasis of the endoplasmic reticulum (ER) during exposure to diverse environmental conditions that cause ER stress. Here we report that the human fungal pathogen Cryptococcus neoformans has evolved a unique UPR pathway composed of an evolutionarily conserved Ire1 protein kinase and a novel bZIP transcription factor encoded by HXL1 (HAC1 and XBP1-Like gene 1). C. neoformans HXL1 encodes a protein lacking sequence homology to any known fungal or mammalian Hac1/Xbp1 protein yet undergoes the UPR-induced unconventional splicing in an Ire1-dependent manner upon exposure to various stresses. The structural organization of HXL1 and its unconventional splicing is widely conserved in C. neoformans strains of divergent serotypes. Notably, both C. neoformans ire1 and hxl1 mutants exhibited extreme growth defects at 37°C and hypersensitivity to ER stress and cell wall destabilization. All of the growth defects of the ire1 mutant were suppressed by the spliced active form of Hxl1, supporting that HXL1 mRNA is a downstream target of Ire1. Interestingly, however, the ire1 and hxl1 mutants showed differences in thermosensitivity, expression patterns for a subset of genes, and capsule synthesis, indicating that Ire1 has both Hxl1-dependent and -independent functions in C. neoformans. Finally, Ire1 and Hxl1 were shown to be critical for virulence of C. neoformans, suggesting UPR signaling as a novel antifungal therapeutic target.

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Published In

PLoS Pathog

DOI

EISSN

1553-7374

Publication Date

August 2011

Volume

7

Issue

8

Start / End Page

e1002177

Location

United States

Related Subject Headings

  • Virology
  • Unfolded Protein Response
  • Mice
  • Fungal Proteins
  • Female
  • Endoplasmic Reticulum
  • Cryptococcus neoformans
  • Cryptococcosis
  • Basic-Leucine Zipper Transcription Factors
  • Animals
 

Citation

APA
Chicago
ICMJE
MLA
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Cheon, S. A., Jung, K.-W., Chen, Y.-L., Heitman, J., Bahn, Y.-S., & Kang, H. A. (2011). Unique evolution of the UPR pathway with a novel bZIP transcription factor, Hxl1, for controlling pathogenicity of Cryptococcus neoformans. PLoS Pathog, 7(8), e1002177. https://doi.org/10.1371/journal.ppat.1002177
Cheon, Seon Ah, Kwang-Woo Jung, Ying-Lien Chen, Joseph Heitman, Yong-Sun Bahn, and Hyun Ah Kang. “Unique evolution of the UPR pathway with a novel bZIP transcription factor, Hxl1, for controlling pathogenicity of Cryptococcus neoformans.PLoS Pathog 7, no. 8 (August 2011): e1002177. https://doi.org/10.1371/journal.ppat.1002177.
Cheon SA, Jung K-W, Chen Y-L, Heitman J, Bahn Y-S, Kang HA. Unique evolution of the UPR pathway with a novel bZIP transcription factor, Hxl1, for controlling pathogenicity of Cryptococcus neoformans. PLoS Pathog. 2011 Aug;7(8):e1002177.
Cheon, Seon Ah, et al. “Unique evolution of the UPR pathway with a novel bZIP transcription factor, Hxl1, for controlling pathogenicity of Cryptococcus neoformans.PLoS Pathog, vol. 7, no. 8, Aug. 2011, p. e1002177. Pubmed, doi:10.1371/journal.ppat.1002177.
Cheon SA, Jung K-W, Chen Y-L, Heitman J, Bahn Y-S, Kang HA. Unique evolution of the UPR pathway with a novel bZIP transcription factor, Hxl1, for controlling pathogenicity of Cryptococcus neoformans. PLoS Pathog. 2011 Aug;7(8):e1002177.

Published In

PLoS Pathog

DOI

EISSN

1553-7374

Publication Date

August 2011

Volume

7

Issue

8

Start / End Page

e1002177

Location

United States

Related Subject Headings

  • Virology
  • Unfolded Protein Response
  • Mice
  • Fungal Proteins
  • Female
  • Endoplasmic Reticulum
  • Cryptococcus neoformans
  • Cryptococcosis
  • Basic-Leucine Zipper Transcription Factors
  • Animals