Showing papers by "Susan Lindquist published in 1992"

Hsp104 is required for tolerance to many forms of stress.

Abstract: Heat-shock proteins (hsps) are induced by many types of stress In Saccharomyces cerevisiae, a mutation in the HSP104 gene, a member of the highly conserved hsp100 gene family, reduces the ability of log-phase fermenting cells to withstand high temperatures after mild, conditioning pretreatments Here, we examine the expression of hsp104 and its importance for survival under many different conditions Hsp104 is expressed at a higher level in respiring cells than in fermenting cells and is required for the unusually high basal thermotolerance of respiring cells Its expression in stationary phase cells and spores is crucial for the naturally high thermotolerance of these cell types and for their long-term viability at low temperatures The protein is of critical importance in tolerance to ethanol and of moderate importance in tolerance to sodium arsenite Thus, the hsp104 mutation establishes the validity of a long-standing hypothesis in the heat-shock field, namely, that hsps have broadly protective functions Further, that a single protein is responsible for tolerance to heat, ethanol, arsenite and long-term storage in the cold indicates that the underlying causes of lethality are similar in an extraordinary variety of circumstances Finally, the protein is of little or no importance in tolerance to copper and cadmium, suggesting that the lethal lesions produced by these agents are fundamentally different from those produced by heat

The consequences of expressing hsp70 in Drosophila cells at normal temperatures.

Abstract: In Drosophila cells, regulatory mechanisms not only act to provide rapid induction of hsp70 during heat shock but also to prevent expression at normal temperatures. To determine whether expression of hsp70 is detrimental to cells growing at normal temperatures, we used heterologous promoters to force expression of the protein in tissue culture cells and in larval salivary glands. Initially, constitutive expression of hsp70 substantially reduces the rate of cell growth. With continued expression, however, growth rates recover. At the same time, the intracellular distribution of hsp70 changes. Immediately after induction, the protein is diffusely distributed throughout the cell, but as growth resumes it coalesces into discrete points of high concentration, which we term hsp70 granules. hsp70 granules are also observed both in wild-type Drosophila tissue culture cells and in salivary glands after extended periods of recovery from heat shock. The protein in these granules appears to be irreversibly inactivated. It cannot be dispersed with a second heat shock, and cells containing these granules do not show thermotolerance. Only partial overlap between hsp70 granules and lysosomes indicates that the granules form independently of lysosomes. We conclude that expression of hsp70 is detrimental to growth at normal temperatures. We suggest that the change in hsp70 distribution, from diffuse to granular, represents a mechanism for controlling the protein's activity by sequestration.

Methods and compositions of genetic stress response systems

Abstract: This invention relates to the identification, isolation, purification and manipulation of genetic stress response systems, and more particularly, to genes and expression products of those genes that are components of those systems. These components may be used to protect against potentially toxic stress factors. Stress factors include heat, alcohol and heavy metal ions. A family of stress protector proteins with apparent molecular weights about 100 kd, the hsp100 proteins, are an aspect of this invention. Other stress protector proteins are also within the scope of this invention to enhance or inhibit biological stress response. Applications of this invention to recombinant DNA technology, to commercial methods of food preparation and processing, and to methods of enhancing the stress response of plants and animals, are presented.