Siebe T. van Genesen

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To assess the consequences of inactivation of heat shock factor 1 (HSF1) during aging, we analyzed the effect of HSF1 K80Q, a mutant unable to bind DNA, and of dnHSF1, a mutant lacking the activation domain, on the transcriptome of cells 6 and 24 h after heat shock. The primary response to heat shock (6 h recovery), of which 30 % was HSF1-dependent, had(More)
To probe the limiting nodes in the chaperoning network which maintains cellular proteostasis, we expressed a dominant negative mutant of heat shock factor 1 (dnHSF1), the regulator of the cytoplasmic proteotoxic stress response. Microarray analysis of non-stressed dnHSF1 cells showed a two- or more fold decrease in the transcript level of 10 genes, amongst(More)
BACKGROUND The heat shock response (HSR) and the unfolded protein response (UPR) are both activated by proteotoxic stress, although in different compartments, and share cellular resources. How these resources are allocated when both responses are active is not known. Insight in possible crosstalk will help understanding the consequences of failure of these(More)
BACKGROUND The aging related decline of heat shock factor-1 (HSF1) signaling may be causally related to protein aggregation diseases. To model such disease, we tried to cripple HSF1 signaling in the Xenopus tadpole. RESULTS Over-expression of heat shock factor binding protein-1 did not inhibit the heat shock response in Xenopus. RNAi against HSF1 mRNA(More)
Mammalian cells respond to a lack of amino acids by activating a transcriptional program with the transcription factor ATF4 as one of the main actors. When cells are faced with cytoplasmic proteotoxic stress, a quite different transcriptional response is mounted, the heat shock response, which is mediated by HSF1. Here, we show that amino acid deprivation(More)
In jawed vertebrates, bc-crystallins are restricted to the eye lens and thus excellent markers of lens evolution. These bc-crystallins are four Greek key motifs/two domain proteins, whereas the urochordate bc-crystallin has a single domain. To trace the origin of the vertebrate bc-crystallin genes, we searched for homologues in the genomes of a jawless(More)
Post-heat shock refolding of luciferase requires chaperones. Expression of a dominant negative HSF1 mutant (dnHSF1), which among other effects depletes cells of HSF1-regulated chaperones, blocked post-heat shock refolding of luciferase targeted to the cytoplasm, nucleus, or peroxisomes, while refolding of endoplasmic reticulum (ER)-targeted luciferase was(More)
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