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S Lindquist

Publications and source records attributed to S Lindquist.

115 records · Page 7Linked to original sources
PubMed1982

The heat shock response is self-regulated at both the transcriptional and posttranscriptional levels.

When Drosophila cells are shifted from 25 degrees C to 37 degrees C, the synthesis of a small group of proteins (the heat shock proteins or HSPs) is rapidly induced, while most preexisting synthesis is repressed. On return to normal growing temperatures, synthesis of HSPs is gradually repressed and normal synthesis is restored. We show that production of HSP 70 (the major heat-induced protein in these cells) is quantitatively correlated with the degree of stress. The level of synthesis is controlled both transcriptionally and posttranscriptionally through repression of HSP 70 mRNA synthesis and destabilization of HSP 70 transcripts. These regulatory mechanisms depend upon the accumulation of the HSPs themselves; when the production of functional HSPs is blocked, HS transcription continues and HS mRNAs are stable, accumulating in vast quantities; if the block is released, a specific quantity of functional HSP must accumulate before HS transcription is repressed and preexisting HS mRNAs are destabilized. Evidence is also presented that indicates that the same quantity of HSP 70 is required to release the block in normal protein synthesis.

Animals↗
PubMed1982

Heat shock and recovery are mediated by different translational mechanisms.

When Drosophila cells are shifted from 25 degrees C to 37 degrees C, protein synthesis is rapidly redirected from the complex pattern characteristic of normal growth to the simple pattern of heat shock proteins (HSPs). On return to 25 degrees C, synthesis of normal proteins is gradually reactivated and that of HSPs is repressed. In quantifying many different recovery experiments, we found that preexisting mRNAs always behaved as a cohort, with messages for different proteins returning to translation at the same rate. Heat shock mRNAs (HS mRNAs), on the other hand, never behaved as a cohort. Their repression was asynchronous, with translation of hsp70 always the first and translation of hsp82 always the last to be repressed. Although recovery times varied enormously (depending on the severity of the heat treatment), repression of hsp70 was always correlated with restoration of normal synthesis, suggesting a link between the two events, hsp70 repression was not simply due to competition with reactivated 25 degrees C mRNAs. A general decline in the translation efficiency of hsp70 mRNA was not observed. Instead, an increasing number of messages were translationally inactivated, while those remaining in the translational pool retained full ribosome loading. Unlike inactive 25 degrees C mRNAs, which are stable during heat shock, inactive HSP mRNAs are degraded during recovery.

Animals↗
PubMed1980

Intracellular localization of heat shock proteins in Drosophila.

When cells and tissues of Drosophila are subjected to elevated temperatures, the pattern of protein synthesis shifts from the production of a broad spectrum of different proteins to the vigorous production of a small number of new, heat shock proteins. The intracellular distribution of these proteins has been investigated through autoradiographic analysis of cells labeled with 3H-leucine at 23 degrees and 37 degrees C. After examining sections of cultured cells from D. melanogaster and polytene cells of D. virilis by electron and light microscopy, we conclude that little (if any) heat shock protein becomes associated with mitochondria, despite the many lines of evidence linking the response to respiratory stress. Confirming earlier reports on the presence of heat shock proteins in nuclei, we find the proteins are very highly concentrated there and that their transport to the nucleus occurs very rapidly. Interestingly, their free concentration in the nuclear sap is extremely low; they are, in fact, quantitatively associated with chromosomes. This association occurs in a nonrandom manner, their concentration in highly condensed chromatin being very low relative to that of other chromosomal loci.

Animals↗
PubMedDate not supplied

Genetic basis of induction and overproduction of chromosomal class I beta-lactamase in nonfastidious gram-negative bacilli.

Pseudomonas and several species of gram-negative enterobacteria produce low levels of chromosomally encoded class I beta-lactamase. The level of synthesis can be greatly increased by the addition of beta-lactam antibiotics into the growth medium. Moreover, mutants overproducing the enzyme arise at a high frequency in these species. The beta-lactamase is encoded by the chromosomal ampC gene, and its induction is governed by the ampR regulatory gene, which encodes an activator of ampC transcription. The ampD gene acts, probably indirectly, as a repressor of beta-lactamase synthesis, and it is in this gene that mutations leading to enzyme overproduction are located.

Chromosomes, Bacterial↗