Exploration of Aspergillus fumigatus Ras pathways for novel antifungal drug targets

Research output: Contribution to journalShort survey

8 Citations (Scopus)

Abstract

Ras pathway signaling is a critical virulence determinant for pathogenic fungi. Localization of Ras to the plasma membrane (PM) is required for Ras network interactions supporting fungal growth and virulence. For example, loss of Aspergillus fumigatus RasA signaling at the PM via inhibition of palmitoylation leads to decreased growth, altered hyphal morphogenesis, decreased cell wall integrity and loss of virulence. In order to be properly localized and activated, Ras proteins must transit a series of post-translational modification (PTM) steps. These steps include farnesylation, proteolytic cleavage of terminal amino acids, carboxymethylation, and palmitoylation. Because Ras activation drives tumor development, Ras pathways have been extensively studied in mammalian cells as a potential target for anti-cancer therapy. Inhibitors of mammalian Ras interactions and PTM components have been, or are actively being, developed. This review will focus on the potential for building upon existing scaffolds to exploit fungal Ras proteins for therapy, synthesizing data from studies employing both mammalian and fungal systems.

Original languageEnglish (US)
Article number128
JournalFrontiers in Microbiology
Volume6
Issue numberFEB
DOIs
StatePublished - Jan 1 2015

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Aspergillus fumigatus
Lipoylation
Virulence
ras Proteins
Post Translational Protein Processing
Cell Membrane
Pharmaceutical Preparations
Prenylation
Fungal Proteins
Growth
Morphogenesis
Cell Wall
Neoplasms
Fungi
Amino Acids
Therapeutics

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Microbiology (medical)

Cite this

Exploration of Aspergillus fumigatus Ras pathways for novel antifungal drug targets. / Al Abdallah, Qusai; Fortwendel, Jarrod.

In: Frontiers in Microbiology, Vol. 6, No. FEB, 128, 01.01.2015.

Research output: Contribution to journalShort survey

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