Pbp1-Interacting Protein Mkt1 Regulates Virulence and Sexual Reproduction in Cryptococcus neoformans.
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The Mkt1-Pbp1 complex promotes mating-type switching by regulating the translation of HO mRNA in Saccharomyces cerevisiae. Here, we performed in vivo immunoprecipitation assays and mass spectrometry analyses in the human fungal pathogen Cryptococcus neoformans to show that Pbp1, a poly(A)-binding protein-binding protein, interacts with Mkt1 containing a PIN like-domain. Association of Pbp1 with Mkt1 was confirmed by co-immunoprecipitation assays. Results of spot dilution growth assays showed that unlike pbp1 deletion mutant strains, mkt1 deletion mutant strains were not resistant to heat stress compared with wild-type. However, similar to the pbp1 deletion mutant strains, the mkt1 deletion mutants exhibited both, defective dikaryotic hyphal production and reduced pheromone gene (MFα1) expression during mating. In addition, deletion of mkt1 caused attenuated virulence in a murine intranasal inhalation model. Taken together, our findings reveal that Mkt1 plays a crucial role in sexual reproduction and virulence in C. neoformans.
Published Version (Please cite this version)10.3389/fcimb.2019.00355
Publication InfoHeitman, Joseph; Cardenas-Corona, Maria; Son, Ye-Eun; Fu, Ci; Jung, Won-Hee; Oh, Sang-Hun; ... Park, Hee-Soo (2019). Pbp1-Interacting Protein Mkt1 Regulates Virulence and Sexual Reproduction in Cryptococcus neoformans. Frontiers in Cellular and Infection Microbiology, 9. pp. 355. 10.3389/fcimb.2019.00355. Retrieved from https://hdl.handle.net/10161/19558.
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Research Professor Emeritus of Molecular Genetics and Microbiology
Research Summary: My lab studies the TORC1 signaling cascade, which senses nutrients and regulates gene expression, translation, and ribosome biogenesis and has been conserved over a billion years of evolution from yeast to humans. The Tor kinase is the target of the anti-proliferative and anti-aging drug rapamycin. The Tor kinases form two evolutionarily conserved multi-protein complexes known as TORC1 and TORC2. We have analyzed in detail the mechanisms of rapamycin
Chair, Department of Molecular Genetics and Microbiology
Signal transduction cascades regulating development and virulence of microorganisms Our research focuses on how cells sense their environment and communicate with other cells. We employ genetic and biochemical approaches to study two divergent single-celled eukaryotic organisms, the yeast Saccharomyces cerevisiae and the pathogenic fungus Cryptococcus neoformans. These organisms both grow as budding yeasts and appear quite similar, yet they have been diverging ov
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