Pleiotropic roles of the msi1-like protein msl1 in Cryptococcus neoformans

Dong Hoon Yang, Shinae Maeng, Anna K. Strain, Anna Floyd, Kirsten Nielsen, Joseph Heitman, Yong Sun Bahn

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7 Citations (Scopus)

Abstract

Msi1-like (MSIL) proteins contain WD40 motifs and have a pleiotropic cellular function as negative regulators of the Ras/cyclic AMP (cAMP) pathway and components of chromatin assembly factor 1 (CAF-1), yet they have not been studied in fungal pathogens. Here we identified and characterized an MSIL protein, Msl1, in Cryptococcus neoformans, which causes life-threatening meningoencephalitis in humans. Notably, Msl1 plays pleiotropic roles in C. neoformans in both cAMP-dependent and -independent manners largely independent of Ras. Msl1 negatively controls antioxidant melanin production and sexual differentiation, and this was repressed by the inhibition of the cAMP-signaling pathway. In contrast, Msl1 controls thermotolerance, diverse stress responses, and antifungal drug resistance in a Ras/cAMP-independent manner. Cac2, which is the second CAF-1 component, appears to play both redundant and distinct functions compared to the functions of Msl1. Msl1 is required for the full virulence of C. neoformans. Transcriptome analysis identified a group of Msl1-regulated genes, which include stress-related genes such as HSP12 and HSP78. In conclusion, this study demonstrates pleiotropic roles of Msl1 in the human fungal pathogen C. neoformans, providing insight into a potential novel antifungal therapeutic target.

Original languageEnglish
Pages (from-to)1482-1495
Number of pages14
JournalEukaryotic Cell
Volume11
Issue number12
DOIs
Publication statusPublished - 2012 Dec

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Molecular Biology

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    Yang, D. H., Maeng, S., Strain, A. K., Floyd, A., Nielsen, K., Heitman, J., & Bahn, Y. S. (2012). Pleiotropic roles of the msi1-like protein msl1 in Cryptococcus neoformans. Eukaryotic Cell, 11(12), 1482-1495. https://doi.org/10.1128/EC.00261-12