Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
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The MSI3 gene was isolated as a multicopy suppressor of the heat shock-sensitive phenotype of the ira1 mutation, which causes hyperactivation of the RAS-cAMP pathway. Overexpression of MSI3 also suppresses the heat shock-sensitive phenotype of the bcy1 mutant. Determination of the DNA sequence of MSI3 revealed that MSI3 can encode a 77.4 kDa protein related to the HSP70 family. The amino acid sequence of Msi3p is about 30% identical to that of the Ssa1p of Saccharomyces cerevisiae. This contrasts with the finding that members of the HSP70 family generally show at least 50% amino acid identity. The consensus nucleotide sequence of the heat shock element (HSE) was found in the upstream region of MSI3. Moreover, the steady-state levels of the MSI3 mRNA and protein were increased upon heat shock. These results indicate that the MSI3 gene encodes a novel HSP70-like heat shock protein. Disruption of the MSI3 gene was associated with a temperature sensitive growth phenotype but unexpectedly, thermotolerance was enhanced in the disruptant.
Mol Gen Genet 1993 Sep
PMID:MSI3, a multicopy suppressor of mutants hyperactivated in the RAS-cAMP pathway, encodes a novel HSP70 protein of Saccharomyces cerevisiae. 841 80

Three related gene families of low-molecular-weight (LMW) heat shock proteins (HSPs) have been characterized in plants. We describe a fourth LMW HSP family, represented by PsHSP22.7 from Pisum sativum and GmHSP22.0 from Glycine max, and demonstrate that this family of proteins is endomembrane localized. PsHSP22.7 and GmHSP22.0 are 76.7% identical at the amino acid level. Both proteins have amino-terminal signal peptides and carboxyl-terminal sequences characteristic of endoplasmic reticulum (ER) retention signals. The two proteins closely resemble class I cytoplasmic LMW HSPs, suggesting that they evolved from the cytoplasmic proteins through the addition of the signal peptide and ER retention motif. The endomembrane localization of these proteins was confirmed by cell fractionation. The polypeptide product of PsHSP22.7 mRNA was processed to a smaller-M(r) form by canine pancreatic microsomes; in vivo, GmHSP22.0 polysomal mRNA was found to be predominantly membrane bound. In vitro-processed PsHSP22.7 corresponded in mass and pI to one of two proteins detected in ER fractions from heat-stressed plants by using anti-PsHSP22.7 antibodies. Like other LMW HSPs, PsHSP22.7 was observed in higher-molecular-weight structures with apparent masses of between 80 and 240 kDa. The results reported here indicate that members of this new class of LMW HSPs are most likely resident ER proteins and may be similar in function to related LMW HSPs in the cytoplasm. Along with the HSP90 and HSP70 classes of HSPs, this is the third category of HSPs localized to the ER.
Mol Cell Biol 1993 Jan
PMID:Localization of small heat shock proteins to the higher plant endomembrane system. 841 29

To understand the function of multiple heat shock transcription factors in higher eukaryotes, we have characterized the interaction of recombinant mouse heat shock transcription factors 1 and 2 (mHSF1 and mHSF2) with their binding site, the heat shock element (HSE). For our analysis, we utilized the human HSP70 HSE, which consists of three perfect 5'-nGAAn-3' sites (1, 3, and 4) and two imperfect sites (2 and 5) arranged as tandem inverted repeats. Recombinant mHSF1 and mHSF2, which exist as trimers in solution, both bound specifically to this HSE and stimulated transcription of a human HSP70-CAT construct in vitro. Footprinting analyses revealed differential binding of mHSF1 and mHSF2 to the HSP70 HSE. Specifically, mHSF1 bound all five pentameric sites, whereas mHSF2 failed to interact with the first site of the HSE but bound to sites 2 to 5. Missing-nucleoside analysis demonstrated that the third and fourth nGAAn sites were essential for mHSF1 and mHSF2 binding. The binding of the initial mHSF1 trimer to the HSE exhibited preference for sites 3, 4, and 5, and then binding of a second trimer occurred at sites 1 and 2. These results suggest that HSF may recognize its binding site through the dyad symmetry of sites 3 and 4 but requires an adjacent site for stable interaction. Our data demonstrate that mHSF1 and mHSF2 bind specifically to the HSE through major groove interactions. Methidiumpropyl-EDTA footprinting revealed structural differences in the first and third repeats of the HSE, suggesting that the DNA is distorted in this region. The possibility that the HSE region is naturally distorted may assist in understanding how a trimer of HSF can bind to what is essentially an inverted repeat binding site.
Mol Cell Biol 1993 Jun
PMID:Mouse heat shock transcription factors 1 and 2 prefer a trimeric binding site but interact differently with the HSP70 heat shock element. 849 56

Evidence suggests an important role for heat shock proteins (HSPs) in the evolution of atherosclerotic necrotic cores. The present study compared normal-appearing and atherosclerotic aortas obtained from control and diet-induced atherosclerotic cynomolgus macaques and from human autopsies, with respect to the localization and content of 70-kDa HSPs (HSP70). The distribution pattern of HSP70 was determined by immunostaining tissue sections with anti-HSP70 monoclonal antibody against both constitutive and inducible isoforms. Changes in HSP70 staining with developing atherosclerosis were quantitated using video morphometry. Total aortic HSP70 content was evaluated by Western blotting tissue homogenates. In both macaque and human aortas, HSP70 staining was homogeneous in normal-appearing regions, but developed a heterogeneous pattern in the presence of atherosclerosis. Immunostaining for three other HSPs (90, 65, and 28 kDa) confirmed the change as HSP-specific. Video morphometry indicated a significant positive association between severity of atherosclerosis and altered patterns of HSP70 staining. However, Western blots detected no difference in total HSP70 content of either human or macaque aortas with plaque progression. The data suggest HSP70 localization changes in aortas during atherosclerosis evolution without affecting overall aortic HSP70 content. Such changes in HSP70 localization may reflect differences in the cellular response and resistance to cytotoxic conditions present within the plaque, which could influence the expansion of necrotic cores.
Exp Mol Pathol 1993 Jun
PMID:Atherosclerosis alters the localization of HSP70 in human and macaque aortas. 851 43

Populations of cells within solid tumours are exposed to low oxygen concentrations. The mechanism by which tumour cells tolerate such hypoxia is unknown but it may parallel responses to other types of cellular stress. We investigated the effect of oxygen on steady state levels of inducible heat shock protein 70 mRNA in cultured human hepatoma cells. Northern blot analysis demonstrated that hypoxia increased HSP 70 mRNA levels within 3 hours, with a transient 12-fold increase at 6 hours compared with normoxia. We also showed that heat shock induced a 20-fold increase in HSP 70 mRNA. This data suggests that HSPs may be important in tumour progression by protecting cells from hypoxic stress.
Biochem Mol Biol Int 1995 Jul
PMID:Hypoxia induces HSP 70 gene expression in human hepatoma (HEP G2) cells. 852 54

We have analysed the expression of heat shock protein 70 (HSP70) and heat shock factor (HSF) gene during maize pollen development, HSFs being the transcriptional activators of hsp genes. In order to eliminate the sporophytic tissues of anthers, we have isolated homogeneous cell populations corresponding to five stages of maize pollen development from microspores to mature pollen. We show that in the absence of heat stress, hsp70 genes are highly expressed late-bicellular pollen as compared to other stages. HSP70 transcripts are significantly accumulated in response to a heat shock at the late microspore stage but to a much lower extent than in vegetative tissues. The latest stages of pollen development, i.e. mid-tricellular and mature pollen, do not exhibit heat-induced accumulation of HSP70 transcripts. Therefore, we analysed the expression of hsf genes throughout pollen development. We demonstrate that at least three hsf genes are expressed in maize and that transcripts corresponding to one hsf gene, whose expression is independent of temperature in somatic as well as in microgametophytic tissues, are present at similar levels throughout pollen development. In addition, we show that the expression of the two other hsf genes is heat-inducible in maize vegetative tissues and is not significantly increased after heat shock at any stage of pollen development. These results indicate that the loss of hsp gene expression at late stages of pollen development is not due to a modification of hsf gene expression at the mRNA level and that hsf gene expression is differentially regulated in vegetative and microgametophytic tissues.
Plant Mol Biol 1995 Nov
PMID:Expression of heat shock factor and heat shock protein 70 genes during maize pollen development. 854 9

Induction of heat shock protein 70 (HSP-70) is associated with inhibition of hormone-sensitive steroidogenesis and interruption of cholesterol translocation to or into the mitochondria. A number of pharmacological and physiological inhibitors of luteal cell function stimulate HSP-70 synthesis via activation of the heat shock transcription factor (HSF). In the present study we address the following questions: 1) is HSP-70 synthesis increased during prostaglandin F2 alpha (PGF2 alpha)-induced luteolysis or natural luteal regression? 2) Does blocking HSP-70 synthesis reverse the inhibition of hormone-sensitive steroidogenesis induced by heat stress and PGF2 alpha? Gel-retardation assays demonstrated HSF activation within 7.5 min after PGF2 alpha (400 micrograms) administered in vivo. Western blotting revealed HSP-70 synthesis by 1 h with higher levels seen at 2 h. The stress response was similarly activated during natural regression of the corpus luteum in rats. Gel retardation assays demonstrated maximal HSF activation 10 days after ovulation. Western blotting showed that HSP-70 levels increased dramatically on this same day and were sustained for several days after the initiation of luteal regression. Inhibition of HSP-70 synthesis was investigated in isolated luteal cells using a cholesteryl-conjugated phosphorothioate antisense oligodeoxynucleotide. The control was an oligodeoxynucleotide with the same base composition, but with scrambled base sequence. Incubation with 3 microM antisense oligodeoxynucleotide for 2 h before a 42 C heat shock prevented synthesis of HSP-70 while up to 4.5 microM control oligodeoxynucleotide had no effect on HSP-70 synthesis in response to heat shock. Preincubation with antisense oligodeoxynucleotide partially reversed heat stress-induced inhibition of LH-stimulated steroidogenesis. More importantly, preincubation with antisense oligodeoxynucleotide also significantly reversed inhibition of cAMP-stimulated steroidogenesis induced by PGF2 alpha. Treatment with control oligodeoxynucleotide did not reverse heat shock or PGF2 alpha inhibition of hormone-dependent steroidogenesis. The findings that the synthesis of HSP-70 coincides with the loss of luteal function and that blocking its synthesis reverses inhibition of hormone-dependent steroidogenesis strongly suggest a role for HSPs as physiological mediators of luteal regression.
Mol Endocrinol 1995 Nov
PMID:Heat shock protein-70 induction mediates luteal regression in the rat. 858 20

The available sequences of genes encoding the enzymes associated with histidine biosynthesis suggest that this is an ancient metabolic pathway that was assembled prior to the diversification of the Bacteria, Archaea, and Eucarya. Paralogous duplications, gene elongation, and fusion events involving different his genes have played a major role in shaping this biosynthetic route. Evidence that the hisA and the hisF genes and their homologous are the result of two successive duplication events that apparently took place before the separation of the three cellular lineages is extended. These two successive gene duplication events as well as the homology between the hisH genes and the sequences encoding the TrpG-type amidotransferases support the idea that during the early stages of metabolic evolution at least parts of the histidine biosynthetic pathway were mediated by enzymes of broader substrate specificities. Maximum likelihood trees calculated for the available sequences of genes encoding these enzymes have been obtained. Their topologies support the possibility of an evolutionary proximity of archaebacteria with low GC Gram-positive bacteria. This observation is consistent with those detected by other workers using the sequences of heat-shock proteins (HSP70), glutamine synthetases, glutamate dehydrogenases, and carbamoylphosphate synthetases.
J Mol Evol 1995 Dec
PMID:Molecular evolution of the histidine biosynthetic pathway. 858 21

The single-copy actin gene of Giardia lamblia lacks introns; it has an average of 58% amino acid identity with the actin of other species; and 49 of its amino acids can be aligned with the amino acids of a consensus sequence of heat shock protein 70. Analysis of the potential RNA secondary structure in the transcribed region of the G. lamblia actin gene and of the single-copy actin gene of nine other species did not reveal any conserved structures. The G. lamblia actin sequence was used to root the phylogenetic trees based on 65 actin protein sequences from 43 species. This tree is congruent with small-subunit rRNA trees in that it shows that oomycetes are not related to higher fungi; that kineto-platid protozoans, green plants, fungi and animals are monophyletic groups; and that the animal and fungal lineages share a more recent common ancestor than either does with the plant lineage. In contrast to small-subunit rRNA trees, this tree shows that slime molds diverged after the plant lineage. The slower rate of evolution of actin genes of slime molds relative to those of plants, fungi, and animals species might be responsible for this incongruent branching.
J Mol Evol 1995 Dec
PMID:The Giardia lamblia actin gene and the phylogeny of eukaryotes. 858 28

We have modified the differential display technique to isolate 3' regions from different members of the wheat HSP70 gene family. An HSP70 gene family-specific degenerate primer was used as a 5' primer in place of the arbitrary primer used in the original technique. We cloned and sequenced three cDNA fragments that were differentially expressed in heat stressed wheat seedlings. Based on the high similarity between predicted translation products of these three sequences and known members of the HSP70 family from plants, these cDNAs were identified as members of the HSP70 gene family. Two of these members appeared distinct in the 3' non-coding region with only 48% identity. Therefore differential display could successfully be used to isolate 3' regions of different members of a multigene family in a relatively short period, even if the members had highly similar protein-coding regions.
Plant Mol Biol 1996 Feb
PMID:Application of modified differential display technique for cloning and sequencing of the 3' region from three putative members of wheat HSP70 gene family. 860 12


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