Biomedical subjects

S L Lindquist

Publications and source records attributed to S L Lindquist.

21 records · Page 2Linked to original sources

PubMed1989

hsp26 of Saccharomyces cerevisiae is related to the superfamily of small heat shock proteins but is without a demonstrable function.

Analysis of the cloned gene confirms that hsp26 of Saccharomyces cerevisiae is a member of the small heat shock protein superfamily. Previous mutational analysis failed to demonstrate any function for the protein. Further experiments presented here demonstrate that hsp26 has no obvious regulatory role and no major effect on thermotolerance. It is possible that the small heat shock protein genes originated as primitive viral or selfish DNA elements.

Amino Acid Sequence↗

PubMed1987

Eukaryotic initiation factor 4D, the hypusine-containing protein, is conserved among eukaryotes.

When mammalian cells are grown in medium containing [3H]spermidine, a single major tritiated protein identical to eukaryotic initiation factor 4D becomes labeled. This protein contains 1 residue/molecule of tritiated hypusine (N epsilon-(4-amino-2-hydroxybutyl)lysine), a rare amino acid which has been found in no other protein. In order to investigate the conservation of this protein, we examined two nonmammalian eukaryotes, the yeast Saccharomyces cerevisiae and the insect Drosophila melanogaster, and the eubacterial prokaryote Escherichia coli for the presence of the hypusine-containing protein. When the eukaryotic cells were grown in the presence of [3H]spermidine, electrophoretic analysis revealed a single labeled protein. In each case, the apparent molecular weight was near 18,000 and the relative pI was approximately 5.2, similar to the hypusine-containing protein of mammals. Amino acid analysis confirmed the presence of tritiated hypusine in each case, and silver staining of two-dimensional polyacrylamide gels demonstrated that, in yeast and fruit flies as in mammals, the protein is relatively abundant. In the eubacterium E. coli, one tritiated protein was predominant, but its molecular weight was 24,000 and we found no evidence that it contained tritiated hypusine. We found no evidence for the existence of the hypusine-containing protein in the archaebacterium Methanococcus voltae. These data suggest that the hypusine-containing protein is conserved among eukaryotes.

Amino Acids↗

PubMed1987

Hypusine formation in eukaryotic initiation factor 4D is not reversed when rates or specificity of protein synthesis is altered.

In mammalian cells, a single major cellular protein (eukaryotic initiation factor 4D) is post-translationally modified by the conversion of a lysine residue into the unusual amino acid hypusine. This modification was reported to occur during mitogen-stimulated growth of lymphocytes but not during quiescence, suggesting that alternative forms of eukaryotic initiation factor 4D might play a role in the regulation of cell growth perhaps through the control of protein synthesis itself (Cooper, H. L., Park, M. H., and Folk, J. E. (1982) Cell 29, 791-797). We took advantage of the drastic changes in translational specificity which occur in heat-shocked cells of Drosophila melanogaster, and of the wide variations in translation rates which occur in response to alterations of growth media in the fungus Saccharomyces cerevisiae, to investigate the relationship between the intracellular level and state of modification of the hypusine-containing protein and the rate and specificity of translation. We also studied whether the hypusine residue in this protein might be subject to further modification or reversion to lysine. Under all conditions examined, the protein was remarkably long-lived. Furthermore, the hypusine persists in this protein as hypusine, without further modification or reversion to lysine. Thus, we observe no correlation between the state of cellular translation and the persistence or reversal of this protein's modification. In addition, the data imply that neither are the state of such key cellular processes as DNA replication, RNA transcription, or carbohydrate metabolism so correlated.

Animals↗