Related Experiment Video
Updated: May 18, 2026

An Integrated Approach for Microprotein Identification and Sequence Analysis
Published on: July 12, 2022
Pleiotropic roles of the Msi1-like protein Msl1 in Cryptococcus neoformans
Dong-Hoon Yang1, Shinae Maeng, Anna K Strain
1Department of Biotechnology, Center for Fungal Pathogenesis, Yonsei University, Seoul, South Korea.
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.
Insights
Msl1, a protein in the human fungal pathogen Cryptococcus neoformans, regulates key functions including stress response, drug resistance, and virulence. This study reveals Msl1 as a potential novel antifungal therapeutic target.
Area of Science:
- Mycology
- Molecular Biology
- Pathogen Biology
Background:
- Msi1-like (MSIL) proteins regulate the Ras/cyclic AMP (cAMP) pathway and chromatin assembly.
- MSIL proteins have not been previously studied in fungal pathogens.
- Cryptococcus neoformans is a human fungal pathogen causing meningoencephalitis.
Purpose of the Study:
- To identify and characterize an MSIL protein, Msl1, in Cryptococcus neoformans.
- To elucidate the pleiotropic roles of Msl1 in C. neoformans.
- To investigate Msl1's contribution to fungal virulence and identify potential therapeutic targets.
Main Methods:
- Identification and characterization of the Msl1 protein in C. neoformans.
- Analysis of Msl1's function in cAMP-dependent and -independent pathways.
- Assessment of Msl1's role in melanin production, sexual differentiation, thermotolerance, stress responses, and antifungal drug resistance.
- Transcriptome analysis to identify Msl1-regulated genes.
- Evaluation of Msl1's contribution to C. neoformans virulence.
Main Results:
- Msl1 exhibits pleiotropic roles in C. neoformans, affecting both cAMP-dependent and -independent processes.
- Msl1 negatively controls melanin production and sexual differentiation, influenced by cAMP signaling.
- Msl1 regulates thermotolerance, stress responses, and antifungal drug resistance independently of Ras/cAMP.
- Msl1 is essential for the full virulence of C. neoformans.
- Transcriptome analysis revealed Msl1 regulates stress-related genes like HSP12 and HSP78.
Conclusions:
- Msl1 plays multifaceted roles in the human fungal pathogen C. neoformans.
- Msl1's functions are partially dependent on and independent of the cAMP pathway.
- Msl1 is crucial for C. neoformans virulence, highlighting its potential as an antifungal therapeutic target.
Related Concept Videos
Role of Septins
Cellular Functions of Septins
Recent studies have revealed the multifaceted roles of septins in various cellular processes such as cytokinesis, ciliogenesis, and neurogenesis. Septins act as scaffolds and...
Mismatch Repair
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
M-Cdk Drives Transition Into Mitosis
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
Protein Complexes with Interchangeable Parts
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order to...
Pleiotropy
Cohesins
Cohesin complexes in Meiotic Division
Meiosis involves two distinct rounds of chromosomal segregation and cell divisions— Meiosis I followed by Meiosis II – producing four daughter cells. Meiosis I includes the separation of homologous...

