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

Research output: Contribution to journalArticle

5 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 1

Fingerprint

Cryptococcus neoformans
Cyclic AMP
Chromatin Assembly Factor-1
Fungal Drug Resistance
Proteins
Sex Differentiation
Meningoencephalitis
Melanins
Gene Expression Profiling
Genes
Virulence
Antioxidants
Therapeutics

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Molecular Biology

Cite this

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
Yang, Dong Hoon ; Maeng, Shinae ; Strain, Anna K. ; Floyd, Anna ; Nielsen, Kirsten ; Heitman, Joseph ; Bahn, Yong Sun. / Pleiotropic roles of the msi1-like protein msl1 in Cryptococcus neoformans. In: Eukaryotic Cell. 2012 ; Vol. 11, No. 12. pp. 1482-1495.
@article{72250c1805574974b4d10ab79fbefb0b,
title = "Pleiotropic roles of the msi1-like protein msl1 in Cryptococcus neoformans",
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.",
author = "Yang, {Dong Hoon} and Shinae Maeng and Strain, {Anna K.} and Anna Floyd and Kirsten Nielsen and Joseph Heitman and Bahn, {Yong Sun}",
year = "2012",
month = "12",
day = "1",
doi = "10.1128/EC.00261-12",
language = "English",
volume = "11",
pages = "1482--1495",
journal = "Eukaryotic Cell",
issn = "1535-9778",
publisher = "American Society for Microbiology",
number = "12",

}

Yang, DH, Maeng, S, Strain, AK, Floyd, A, Nielsen, K, Heitman, J & Bahn, YS 2012, 'Pleiotropic roles of the msi1-like protein msl1 in Cryptococcus neoformans', Eukaryotic Cell, vol. 11, no. 12, pp. 1482-1495. https://doi.org/10.1128/EC.00261-12

Pleiotropic roles of the msi1-like protein msl1 in Cryptococcus neoformans. / Yang, Dong Hoon; Maeng, Shinae; Strain, Anna K.; Floyd, Anna; Nielsen, Kirsten; Heitman, Joseph; Bahn, Yong Sun.

In: Eukaryotic Cell, Vol. 11, No. 12, 01.12.2012, p. 1482-1495.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Pleiotropic roles of the msi1-like protein msl1 in Cryptococcus neoformans

AU - Yang, Dong Hoon

AU - Maeng, Shinae

AU - Strain, Anna K.

AU - Floyd, Anna

AU - Nielsen, Kirsten

AU - Heitman, Joseph

AU - Bahn, Yong Sun

PY - 2012/12/1

Y1 - 2012/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84870397709&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84870397709&partnerID=8YFLogxK

U2 - 10.1128/EC.00261-12

DO - 10.1128/EC.00261-12

M3 - Article

C2 - 23042129

AN - SCOPUS:84870397709

VL - 11

SP - 1482

EP - 1495

JO - Eukaryotic Cell

JF - Eukaryotic Cell

SN - 1535-9778

IS - 12

ER -

Yang DH, Maeng S, Strain AK, Floyd A, Nielsen K, Heitman J et al. Pleiotropic roles of the msi1-like protein msl1 in Cryptococcus neoformans. Eukaryotic Cell. 2012 Dec 1;11(12):1482-1495. https://doi.org/10.1128/EC.00261-12