The GRR1 gene of Candida albicans is involved in the negative control of pseudohyphal morphogenesis

Butler, David K.; All, Ojay; Goffena, Joy; Loveless, Timothy; Wilson, T. G. J.; Toenjes, Kurt A.

doi:10.1016/j.fgb.2006.03.004

Cited by 39 publications

(35 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Depletion of the G 1 cyclin Cln3p, on the other hand, resulted in a G 1 phase arrest in yeast cells and subsequent development of hyphae and pseudohyphae (7,22), supporting a link between G 1 phase and hyphal development. Depletion of Cln3p in S. cerevisiae, on the other hand, did not activate development (27,59), and blocking/delaying other cell cycle stages in C. albicans did not result in true hyphae (1,5,6,10,13,14,18,47,68,75,80,83).…”

mentioning

confidence: 88%

G ₁ /S Transcription Factor Orthologues Swi4p and Swi6p Are Important but Not Essential for Cell Proliferation and Influence Hyphal Development in the Fungal Pathogen Candida albicans

et al. 2011

View full text Add to dashboard Cite

The G 1 /S transition is a critical control point for cell proliferation and involves essential transcription complexes termed SBF and MBF in Saccharomyces cerevisiae or MBF in Schizosaccharomyces pombe. In the fungal pathogen Candida albicans, G 1 /S regulation is not clear. To gain more insight into the G 1 /S circuitry, we characterized Swi6p, Swi4p and Mbp1p, the closest orthologues of SBF (Swi6p and Swi4p) and MBF (Swi6p and Mbp1p) components in S. cerevisiae. The mbp1⌬/⌬ cells showed minor growth defects, whereas swi4⌬/⌬ and swi6⌬/⌬ yeast cells dramatically increased in size, suggesting a G 1 phase delay. Gene set enrichment analysis (GSEA) of transcription profiles revealed that genes associated with G 1 /S phase were significantly enriched in cells lacking Swi4p and Swi6p. These expression patterns suggested that Swi4p and Swi6p have repressing as well as activating activity. Intriguingly, swi4⌬/⌬ swi6⌬/⌬ and swi4⌬/⌬ mbp1⌬/⌬ strains were viable, in contrast to the situation in S. cerevisiae, and showed pleiotropic phenotypes that included multibudded yeast, pseudohyphae, and intriguingly, true hyphae. Consistently, GSEA identified strong enrichment of genes that are normally modulated during C. albicans-host cell interactions. Since Swi4p and Swi6p influence G 1 phase progression and SBF binding sites are lacking in the C. albicans genome, these factors may contribute to MBF activity. Overall, the data suggest that the putative G 1 /S regulatory machinery of C. albicans contains novel features and underscore the existence of a relationship between G 1 phase and morphogenetic switching, including hyphal development, in the pathogen.

show abstract

mentioning

confidence: 88%

G ₁ /S Transcription Factor Orthologues Swi4p and Swi6p Are Important but Not Essential for Cell Proliferation and Influence Hyphal Development in the Fungal Pathogen Candida albicans

et al. 2011

View full text Add to dashboard Cite

show abstract

“…A ⌬grr1 strain of C. albicans exhibits pseudohyphal growth under yeastlike growth-inducing conditions and does not grow on glucose (123). The constitutive pseudohyphal growth phenotype (27) of the ⌬grr1 deletion strain could be explained by the stabilization of the two G 1 cyclins Ccn1 and Cln3. That Grr1 mediates degradation of Ccn1 and Cln3 was demonstrated by the fact that both cyclins are stabilized; additionally, Cln3 was found as a hyperphosphorylated protein in the ⌬grr1 strain.…”

Section: Grr1 and The Cell Cyclementioning

confidence: 99%

Lessons from Fungal F-Box Proteins

Jonkers

Rep

2009

Eukaryot Cell

View full text Add to dashboard Cite

“…Studies revealed that Grr1 is involved in cell cycle regulation (26,27), nutrient sensing (28,29), and fungal morphogenesis. Grr1 homologs in other fungi, including Candida albicans (Grr1) (30), Aspergillus nidulans (GrrA) (31), and Gibberella zeae (Fbp1) (32), have also been reported. Another F-box protein, Cdc4, has also been studied in both S. cerevisiae (33)(34)(35) and C. albicans (36)(37)(38).…”

mentioning

confidence: 98%

Fbp1-Mediated Ubiquitin-Proteasome Pathway Controls Cryptococcus neoformans Virulence by Regulating Fungal Intracellular Growth in Macrophages

Liu

Xue

2014

Infect Immun

View full text Add to dashboard Cite

Cryptococcus neoformans is a human fungal pathogen that often causes lung and brain infections in immunocompromised patients, with a high fatality rate. Our previous results showed that an F-box protein, Fbp1, is essential for Cryptococcus virulence independent of the classical virulence factors, suggesting a novel virulence control mechanism. In this study, we show that Fbp1 is part of the ubiquitin-proteasome system, and we further investigated the mechanism of Fbp1 function during infection. Time course studies revealed that the fbp1⌬ mutant causes little damage in the infected lung and that the fungal burden in the lung remains at a low but persistent level throughout infection. The fbp1⌬ mutant cannot disseminate to other organs following pulmonary infection in the murine inhalation model of cryptococcosis but still causes brain infection in a murine intravenous injection model, suggesting that the block of dissemination of the fbp1⌬ mutant is due to its inability to leave the lung. The fbp1⌬ mutant showed a defect in intracellular proliferation after phagocytosis in a Cryptococcus-macrophage interaction assay, which likely contributes to its virulence attenuation. To elucidate the molecular basis of the SCF(Fbp1) E3 ligase function, we analyzed potential Fbp1 substrates based on proteomic approaches combined with phenotypic analysis. One substrate, the inositol phosphosphingolipid-phospholipase C1 (Isc1), is required for fungal survival inside macrophage cells, which is consistent with the role of Fbp1 in regulating Cryptococcus-macrophage interaction and fungal virulence. Our results thus reveal a new determinant of fungal virulence that involves the posttranslational regulation of inositol sphingolipid biosynthesis.C ryptococcus neoformans is a major human fungal pathogen and the causative agent of fatal cryptococcal meningoencephalitis, which is considered an AIDS-defined condition (1-5). Despite its medical importance, the treatment for cryptococcosis is limited. With increasing concerns of drug resistance and evolution of new virulent strains (6-9), there is an urgent need to understand the molecular basis of cryptococcal infection in order to discover and develop safer and more effective antifungal drugs. Against this background of clinical need are the heroic research efforts toward understanding the mechanism of Cryptococcus development and virulence that have significantly advanced the field in the past several decades. Several virulence factors, including production of polysaccharide capsule and melanin and the ability to grow at body temperature (37°C), have been well characterized (10, 11). A number of signal pathways regulating these virulence factors and important for Cryptococcus pathogenesis have also been identified (5, 12-16). Systematic genetic analysis of genes involved in fungal virulence revealed a capsule-independent antiphagocytic mechanism, as well as a number of proteins regulating fungal virulence independent of the classical virulence factors (17, 18). These studies revealed tha...

show abstract

The GRR1 gene of Candida albicans is involved in the negative control of pseudohyphal morphogenesis

Cited by 39 publications

References 54 publications

G ₁ /S Transcription Factor Orthologues Swi4p and Swi6p Are Important but Not Essential for Cell Proliferation and Influence Hyphal Development in the Fungal Pathogen Candida albicans

G ₁ /S Transcription Factor Orthologues Swi4p and Swi6p Are Important but Not Essential for Cell Proliferation and Influence Hyphal Development in the Fungal Pathogen Candida albicans

Lessons from Fungal F-Box Proteins

Fbp1-Mediated Ubiquitin-Proteasome Pathway Controls Cryptococcus neoformans Virulence by Regulating Fungal Intracellular Growth in Macrophages

Contact Info

Product

Resources

About

The GRR1 gene of Candida albicans is involved in the negative control of pseudohyphal morphogenesis

Cited by 39 publications

References 54 publications

G 1 /S Transcription Factor Orthologues Swi4p and Swi6p Are Important but Not Essential for Cell Proliferation and Influence Hyphal Development in the Fungal Pathogen Candida albicans

G 1 /S Transcription Factor Orthologues Swi4p and Swi6p Are Important but Not Essential for Cell Proliferation and Influence Hyphal Development in the Fungal Pathogen Candida albicans

Lessons from Fungal F-Box Proteins

Fbp1-Mediated Ubiquitin-Proteasome Pathway Controls Cryptococcus neoformans Virulence by Regulating Fungal Intracellular Growth in Macrophages

Contact Info

Product

Resources

About

G ₁ /S Transcription Factor Orthologues Swi4p and Swi6p Are Important but Not Essential for Cell Proliferation and Influence Hyphal Development in the Fungal Pathogen Candida albicans

G ₁ /S Transcription Factor Orthologues Swi4p and Swi6p Are Important but Not Essential for Cell Proliferation and Influence Hyphal Development in the Fungal Pathogen Candida albicans