In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 103, No. 3 ( 2006-01-17), p. 726-731
Abstract:
A better understanding of the molecular basis of programmed cell death (PCD) in fungi could provide information that is useful in the design of antifungal drugs that combat life-threatening fungal infections. Harsh environmental stresses, such as acetic acid or hydrogen peroxide, have been shown to induce PCD in the pathogenic fungus Candida albicans . In this study, we show that dying cells progress from an apoptotic state to a secondary necrotic state and that the rate at which this change occurs is proportional to the intensity of the stimulus. Also, we found that the temporal response is modulated by Ras–cAMP–PKA signals. Mutations that block Ras–cAMP–PKA signaling ( ras1 Δ, cdc35 Δ, tpk1 Δ, and tpk2 Δ) suppress or delay the apoptotic response, whereas mutations that stimulate signaling ( RAS1 val13 and pde2 Δ) accelerate the rate of entry of cells into apoptosis. Pharmacological stimulation or inhibition of Ras signaling reinforces these findings. Transient increases in endogenous cAMP occur under conditions that stimulate apoptosis but not growth arrest. Death-specific changes in the abundance of different isoforms of the PKA regulatory subunit, Bcy1p, are also observed. Activation of Ras signals may regulate PCD of C. albicans , either by inhibiting antiapoptotic functions (such as stress responses) or by activating proapoptotic functions.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.0506405103
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2006
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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