Pleiotropic roles of the Msi1-like protein Msl1 in Cryptococcus neoformans.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Yang, D-H; Maeng, S; Strain, AK; Floyd, A; Nielsen, K; Heitman, J; Bahn, Y-S

Published Date

  • December 2012

Published In

Volume / Issue

  • 11 / 12

Start / End Page

  • 1482 - 1495

PubMed ID

  • 23042129

Pubmed Central ID

  • PMC3536287

Electronic International Standard Serial Number (EISSN)

  • 1535-9786

Digital Object Identifier (DOI)

  • 10.1128/EC.00261-12


  • eng

Conference Location

  • United States