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Maeng, Shinae,Ko, Young-Joon,Kim, Gyu-Bum,Jung, Kwang-Woo,Floyd, Anna,Heitman, Joseph,Bahn, Yong-Sun American Society for Microbiology 2010 EUKARYOTIC CELL Vol.9 No.3
<B>ABSTRACT</B><P>The cyclic AMP (cAMP) pathway plays a central role in the growth, differentiation, and virulence of pathogenic fungi, including Cryptococcus neoformans. Three upstream signaling regulators of adenylyl cyclase (Cac1), Ras, Aca1, and Gpa1, have been demonstrated to control the cAMP pathway in C. neoformans, but their functional relationship remains elusive. We performed a genome-wide transcriptome analysis with a DNA microarray using the <I>ras1</I>Δ, <I>gpa1</I>Δ, <I>cac1</I>Δ, <I>aca1</I>Δ, and <I>pka1</I>Δ <I>pka2</I>Δ mutants. The <I>aca1</I>Δ, <I>gpa1</I>Δ, <I>cac1</I>Δ, and <I>pka1</I>Δ <I>pka2</I>Δ mutants displayed similar transcriptome patterns, whereas the <I>ras1</I>Δ mutant exhibited transcriptome patterns distinct from those of the wild type and the cAMP mutants. Interestingly, a number of environmental stress response genes are modulated differentially in the <I>ras1</I>Δ and cAMP mutants. In fact, the Ras signaling pathway was found to be involved in osmotic and genotoxic stress responses and the maintenance of cell wall integrity via the Cdc24-dependent signaling pathway. Notably, the Ras and cAMP mutants exhibited hypersensitivity to a polyene drug, amphotericin B, without showing effects on ergosterol biosynthesis, which suggested a novel method of antifungal combination therapy. Among the cAMP-dependent gene products that we characterized, two small heat shock proteins, Hsp12 and Hsp122, were found to be involved in the polyene antifungal drug susceptibility of C. neoformans.</P>
Mini review : Msi1-Like (MSIL) Proteins in Fungi
( Dong Hoon Yang ),( Shinae Maeng ),( Yong Sun Bahn ) 한국균학회 2013 Mycobiology Vol.41 No.1
Msi1-like (MSIL) proteins, which are eukaryote-specific and contain a series of WD40 repeats, have pleiotropic roles in chromatin assembly, DNA damage repair, and regulation of nutrient/stress-sensing signaling pathways. In the fungal kingdom, the functions of MSIL proteins have been studied most intensively in the budding yeast model Saccharomyces cerevisiae, an ascomycete. Yet their functions are largely unknown in other fungi. Recently, an MSIL protein, Msl1, was discovered and functionally characterized in the pathogenic yeast Cryptococcus neoformans, a basidiomycete. Interestingly, MSIL proteins appear to have redundant and unique roles in both fungi, suggesting that MSIL proteins may have evolutionarily divergent roles in different parts of the fungal kingdom. In this review, we will describe the current findings regarding the role of MSIL proteins in fungi and discuss future directions for research on this topic.
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 American Society for Microbiology 2012 EUKARYOTIC CELL Vol.11 No.12
<B>ABSTRACT</B><P> 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 <I>HSP12</I> and <I>HSP78</I> . 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. </P>