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Showing papers by "Susan Lindquist published in 1990"


Journal ArticleDOI
01 Jun 1990-Science
TL;DR: It is demonstrated that a particular heat shock protein plays a critical role in cell survival at extreme temperatures and is rescued with the wild-type gene.
Abstract: A heat shock protein gene, HSP104, was isolated from Saccharomyces cerevisiae and a deletion mutation was introduced into yeast cells. Mutant cells grew at the same rate as wild-type cells and died at the same rate when exposed directly to high temperatures. However, when given a mild pre-heat treatment, the mutant cells did not acquire tolerance to heat, as did wild-type cells. Transformation with the wild-type gene rescued the defect of mutant cells. The results demonstrate that a particular heat shock protein plays a critical role in cell survival at extreme temperatures.

826 citations


Journal ArticleDOI
08 Nov 1990-Nature
TL;DR: This work has taken advantage of the capacity of mammalian steroid receptors to function in yeast and constructed a strain of Saccharomyces cerevisiae in which hsp90 expression was regulatable and could be reduced more than 20-fold relative to wild type, providing the first biological evidence that hSp90 acts in the signal transduction pathway for steroid receptors.
Abstract: Signalling by steroid hormones is mediated by receptor proteins that bind hormonal ligands and regulate the transcription of specific genes. The heat-shock protein hsp90 seems to associate selectively with unliganded receptors (aporeceptors), but it has not been determined whether this interaction affects receptor function in vivo. To address the role of hsp90, we have taken advantage of the capacity of mammalian steroid receptors to function in yeast. We constructed a strain of Saccharomyces cerevisiae in which hsp90 expression was regulatable and could be reduced more than 20-fold relative to wild type. At low levels of hsp90, aporeceptors seem to be mostly hsp90-free, yet fail to enhance transcription; on hormone addition, the receptors are activated but with markedly reduced efficiency. Thus hsp90 does not inhibit receptor function solely by steric interference; rather, hsp90 seems to facilitate the subsequent response of the aporeceptor to the hormonal signal. This is the first biological evidence that hsp90 acts in the signal transduction pathway for steroid receptors.

788 citations


Journal ArticleDOI
01 Jan 1990
TL;DR: Current knowledge is reviewed of two cytoplasmic mechanisms employed during the response in the fruit fly Drosophila melanogaster that are very stable and accumulate in large numbers during heat shock.
Abstract: The rapid and dramatic induction of heat-shock proteins is accomplished by regulatory mechanisms acting at many different levels. Here we review current knowledge of two cytoplasmic mechanisms employed during the response in the fruit fly Drosophila melanogaster. (1) Heat-shock messages are translated with high efficiency during heat shock while most normal cellular messages are inactive. Sequences in the 5'-untranslated leader of heat shock mRNAs govern their preferential translation. (2) The messages for heat-shock proteins are unstable at normal temperatures. During heat shock, however, they are very stable and accumulate in large numbers. Sequences in their 3'-untranslated regions play a major role in determining their stability.

83 citations


Journal ArticleDOI
TL;DR: It is proposed that basal repression and heat-induced depression of transcription play major roles in regulating the expression of HSP26, the small heat shock protein of Saccharomyces cerevisiae.
Abstract: hsp26, the small heat shock protein of Saccharomyces cerevisiae, accumulates in response to heat and other types of stress. It also accumulates during the normal course of development, as cells enter stationary phase growth or begin to sporulate (S. Kurtz, J. Rossi, L. Petko, and S. Lindquist, Science 231:1154-1157, 1986). Analysis of deletion and insertion mutations demonstrated that transcriptional control plays a critical role in regulating HSP26 expression. The HSP26 promoter was found to be complex and appears to contain repressing elements as well as activating elements. Several upstream deletion mutations resulted in strong constitutive expression of HSP26. Furthermore, upstream sequences from the HSP26 gene repressed the constitutive expression of a heterologous heat shock gene. We propose that basal repression and heat-induced depression of transcription play major roles in regulating the expression of HSP26. None of the recombinant constructs that we analyzed separated cis-regulatory sequences responsible for heat shock regulation from those responsible for developmental regulation of HSP26. Depression of HSP26 transcription may be the general mechanism of HSP26 induction in yeast cells. This regulatory scheme is very different from that described for the regulation of most other heat shock genes.

52 citations


Journal ArticleDOI
TL;DR: Considering the extremely ancient nature of the heat shock response and the extraordinary variety of organisms and cell types in which it is found, it is not surprising that several different mechanisms have evolved to ensure that the hsps will be produced as rapidly as possible after a shift to high temperature.
Abstract: I. INTRODUCTION All cells respond to temperatures above their normal growth temperatures by inducing the synthesis of a small group of evolutionarily conserved polypeptides known as the heat shock proteins (hsps). Some of the hsps are required to help cells grow at the upper end of their normal temperature range, others to help cells withstand the toxic effects of more extreme temperatures. Many of the proteins are also produced at normal temperatures or have close relatives that are produced at normal temperatures (the “heat shock cognate” proteins). The hsps and their relatives participate in an extraordinary variety of cellular processes, including DNA synthesis, protein secretion, the response to steroid hormones, and the “chaperoning” of newly synthesized proteins. The variety and complexity of these interactions are only beginning to be unraveled. What defines the hsps as a group, however, is the immediate and very dramatic increase in their synthesis when cells are exposed to higher temperatures (Lindquist and Craig 1988). Considering the extremely ancient nature of the heat shock response and the extraordinary variety of organisms and cell types in which it is found, it is not surprising that several different mechanisms have evolved to ensure that the hsps will be produced as rapidly as possible after a shift to high temperature. In all organisms investigated, transcriptional regulation plays an important role in the induction of the hsps. In eukaryotes, a heat-shock-activated transcription factor binds to a promoter/enhancer element that provides heat-inducible transcription (for review, see Chapters 17 and 18). In...

31 citations


Book ChapterDOI
01 Jan 1990
TL;DR: Many organisms face the challenge of a changing environment and have developed the ability to mount transient responses in which subsets of genes appropriate to current conditions are activated for an appropriate time.
Abstract: Many organisms face the challenge of a changing environment. Individual cells in a multicellular organism face similar challenges. To cope with this, cells and organisms have developed the ability to mount transient responses in which subsets of genes appropriate to current conditions are activated for an appropriate time. One particularly well studied example of a transient response is provided by the heat-shock response (for general reviews see Lindquist, 1986; Lindquist and Craig, 1988). This induction of a small number of highly conserved proteins (known as the heat shock proteins or hsps) occurs when cultured cells or whole organisms are exposed to temperatures above their normal growth range. When the cells or organisms are returned to normal temperatures normal patterns of synthesis are restored.

7 citations