title: The unfolded protein response (UPR) pathway in Cryptococcus.
abstract: Unique and evolutionarily conserved signaling pathways allow an organism to sense, respond to, and adapt to internal and external environmental cues at its biological niche. In eukaryotic cells, the unfolded protein response (UPR) pathway regulates endoplasmic reticulum (ER) homeostasis upon exposure to environmental changes causing ER stress. The UPR pathway of Cryptococcus neoformans, an opportunistic fungal pathogen, which causes life-threatening meningoencephalitis in immunocompromised individuals, consists of the evolutionarily conserved Ire1 kinase, a unique bZIP transcription factor, Hxl1, and the ER-resident molecular chaperone Kar2/BiP. Although the Cryptococcus UPR pathway regulates ER stress, antifungal drug resistance, and virulence in an Ire1/Hxl1-dependent manner, Ire1 has Hxl1-independent roles in capsule biosynthesis and thermotolerance. In this review, we highlight the conserved and unique features of the Cryptococcus UPR pathway compared with other fungal UPR systems and its importance in the pathogenesis of cryptococcosis and discuss future challenges in this field.
authors: Department of Life Science; Research Center for Biomolecules and Biosystems; College of Natural Science; Chung-Ang University; Seoul, Korea; Department of Agricultural Biotechnology and Center for Fungal Pathogenesis; Seoul National University; Seoul, Korea.
authors: Seon Ah
authors: SA
authors: Cheon
authors: Department of Biotechnology; Center for Fungal Pathogenesis; Yonsei University; Seoul, Korea.
authors: Kwang-Woo
authors: KW
authors: Jung
authors: Department of Biotechnology; Center for Fungal Pathogenesis; Yonsei University; Seoul, Korea.
authors: Yong-Sun
authors: YS
authors: Bahn
authors: Department of Life Science; Research Center for Biomolecules and Biosystems; College of Natural Science; Chung-Ang University; Seoul, Korea.
authors: Hyun Ah
authors: HA
authors: Kang
mesh_terms: D003455:Cryptococcus neoformans / Q000378:metabolism / Q000472:pathogenicity / Q000502:physiology*; D025141:Drug Resistance, Fungal; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000502:physiology*; D005656:Fungal Proteins / Q000378:metabolism; D006801:Humans; D013312:Stress, Physiological; D056811:Unfolded Protein Response; D014774:Virulence
chemical_list: D005656:Fungal Proteins
keywords: Cryptococcus neoformans; ER stress; Hxl1; Ire1; unfolded protein response