title: Involvement of yeast HSP90 isoforms in response to stress and cell death induced by acetic acid.
abstract: Acetic acid-induced apoptosis in yeast is accompanied by an impairment of the general protein synthesis machinery, yet paradoxically also by the up-regulation of the two isoforms of the heat shock protein 90 (HSP90) chaperone family, Hsc82p and Hsp82p. Herein, we show that impairment of cap-dependent translation initiation induced by acetic acid is caused by the phosphorylation and inactivation of eIF2α by Gcn2p kinase. A microarray analysis of polysome-associated mRNAs engaged in translation in acetic acid challenged cells further revealed that HSP90 mRNAs are over-represented in this polysome fraction suggesting preferential translation of HSP90 upon acetic acid treatment. The relevance of HSP90 isoform translation during programmed cell death (PCD) was unveiled using genetic and pharmacological abrogation of HSP90, which suggests opposing roles for HSP90 isoforms in cell survival and death. Hsc82p appears to promote survival and its deletion leads to necrotic cell death, while Hsp82p is a pro-death molecule involved in acetic acid-induced apoptosis. Therefore, HSP90 isoforms have distinct roles in the control of cell fate during PCD and their selective translation regulates cellular response to acetic acid stress.
authors: Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Braga, Portugal.
authors: Alexandra
authors: A
authors: Silva
authors: Belém
authors: B
authors: Sampaio-Marques
authors: Angela
authors: A
authors: Fernandes
authors: Laura
authors: L
authors: Carreto
authors: Fernando
authors: F
authors: Rodrigues
authors: Martin
authors: M
authors: Holcik
authors: Manuel A S
authors: MA
authors: Santos
authors: Paula
authors: P
authors: Ludovico
mesh_terms: D019342:Acetic Acid / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000187:drug effects; D020033:Protein Isoforms; D013312:Stress, Physiological / Q000187:drug effects; D015003:Yeasts / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*
chemical_list: D018841:HSP90 Heat-Shock Proteins; D020033:Protein Isoforms; D019342:Acetic Acid
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