Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have isolated a human genomic clone that encodes the glucose-responsive protein GRP78 and have used this cloned gene probe, together with a cloned HSP70 gene, to study the expression of both stress-induced genes in response to inhibitors of cellular metabolism. On the basis of the effects of this group of chemicals on GRP78 and HSP70 expression, we have identified three classes of stress gene inducers. The first class induces GRP78 expression and includes inhibitors of glycoprotein processing. The second class results in coordinate activation of both GRP78 and HSP70 synthesis and includes amino acid analogs and heavy metals. Chemicals in the third class coordinately induce GRP78 and repress HSP70 expression; this class includes the calcium ionophore A23187 and the glucose analog 2-deoxyglucose. Whereas induction of GRP78 or HSP70 expression is primarily due to transcriptional activation, chemicals that repress HSP70 expression act through posttranscriptional regulation. These results reveal that the regulation of GRP78 and HSP70 expression is complex and may be dependent on the specificity and magnitude of physiological damage.
Mol Cell Biol 1988 Jan
PMID:Complex regulation of heat shock- and glucose-responsive genes in human cells. 327 76

To identify the regulatory elements of the human thymidine kinase (TK) gene, we have established stable cell lines carrying different chimeric constructs of the TK gene. Our results can be summarized as follows. (i) When the TK coding sequence is under the control of the calcyclin promoter (a promoter that is activated when G0 cells are stimulated by growth factors), TK mRNA levels are higher in G1-arrested cells than in proliferating cells; (ii) when the TK coding sequence is under the control of the promoter of heat shock protein HSP70, steady-state levels of TK mRNA are highest after heat shock, regardless of the position of the cells in the cell cycle; (iii) the bacterial CAT gene under the control of the human TK promoter is maximally expressed in the S phase; (iv) the TK cDNA driven by the simian virus 40 promoter is also maximally expressed in the S phase; and (v) TK enzyme activity is always at a maximum in the S phase, even when the levels of TK mRNA are highest in nonproliferating cells. We conclude that although the TK coding sequence may also play some role, the TK promoter has an important role in the cell cycle regulation of TK mRNA levels.
Mol Cell Biol 1988 Apr
PMID:Role of the promoter in the regulation of the thymidine kinase gene. 338 89

A unique member of the mouse HSP70 gene family has been isolated and characterized with respect to its DNA sequence organization and expression. The gene contains extensive similarity to a heat shock-inducible HSP70 gene within the coding region but diverges in both 3' and 5' nontranslated regions. The gene does not yield transcripts in response to heat shock in mouse L cells. Rather, the gene appears to be activated uniquely in the male germ line. Analysis of RNA from different developmental stages and from enriched populations of spermatogenic cells revealed that this gene is expressed during the prophase stage of meiosis. A transcript different in size from the major heat-inducible mouse transcripts is most abundant in meiotic prophase spermatocytes and decreases in abundance in postmeiotic stages of spermatogenesis. This pattern of expression is distinct from that observed for another member of this gene family, which was previously shown to be expressed abundantly in postmeiotic germ cells. These observations suggest that specific HSP70 gene family members play distinct roles in the differentiation of the germ cell lineage in mammals.
Mol Cell Biol 1988 Jul
PMID:Identification and sequence analysis of a new member of the mouse HSP70 gene family and characterization of its unique cellular and developmental pattern of expression in the male germ line. 340 24

We have examined the posttranscriptional regulation of hsp70 gene expression in two human cell lines, HeLa and 293 cells, which constitutively express high levels of HSP70. HSP70 mRNA translates with high efficiency in both control and heat-shocked cells. Therefore, heat shock is not required for the efficient translation of HSP70 mRNA. Rather, the main effect of heat shock on translation is to suppress the translatability of non-heat shock mRNAs. Heat shock, however, has a marked effect on the stability of HSP70 mRNA; in non-heat-shocked cells the half-life of HSP70 mRNA is approximately 50 min, and its stability increases at least 10-fold upon heat shock. Moreover, HSP70 mRNA is more stable in cells treated with protein synthesis inhibitors, suggesting that a heat shock-sensitive labile protein regulates its turnover. An additional effect on posttranscriptional regulation of hsp70 expression can be found in adenovirus-infected cells, in which HSP70 mRNA levels decline precipititously late during infection although hsp70 transcription continues unabated.
Mol Cell Biol 1987 Dec
PMID:Posttranscriptional regulation of hsp70 expression in human cells: effects of heat shock, inhibition of protein synthesis, and adenovirus infection on translation and mRNA stability. 343 93

The HSP70 family of heat-shock proteins constitutes the major proteins synthesized in response to elevated temperatures and other forms of stress. In eukaryotes members of the HSP70 family also include a protein similar if not identical to bovine brain uncoating ATPase and glucose-regulated proteins. An intriguing relation has been established between expression of heat-shock proteins and transformation in mammalian cells. Elevated levels of HSP70 are found in some transformed cell lines, and viral and cellular gene products that are capable of transforming cells in vitro can also stimulate transcription of HSP70 genes. To determine the organization of this complex multigene family in the human genome, we used complementary approaches: Southern analysis and protein gels of Chinese hamster-human somatic cell hybrids, and in situ hybridization to human chromosomes. We demonstrate that functional genes encoding HSP70 proteins map to human chromosomes 6, 14, 21, and at least one other chromosome.
Somat Cell Mol Genet 1987 Mar
PMID:Chromosomal location of human genes encoding major heat-shock protein HSP70. 347 Sep 51

Expression of the human gene encoding the major heat shock protein, HSP70, was induced during cell growth by serum stimulation and after infection with adenovirus 5. In this study we showed that HSP70 gene expression could be induced by adenovirus 5 infection, even in the absence of exogenous serum factors. Whereas serum stimulation induced the expression of the endogenous HSP70 gene, it had no effect on early adenovirus promoters. However, expression of both the cellular HSP70 gene and the adenovirus E3 promoter were activated during adenovirus infection. By using a collection of reconstructed mutant viruses, we identified the 13S product of the E1A region as the specific transcriptional trans-activator of the HSP70 gene.
Mol Cell Biol 1986 Aug
PMID:The E1A 13S product of adenovirus 5 activates transcription of the cellular human HSP70 gene. 349 Dec 95

A factor found in nuclear extracts of human cells bound to the heat shock element of a human heat shock protein 70 gene. The level of this factor was significantly increased after heat shock. This induction was rapid and was not blocked by cycloheximide, suggesting that an initial event in the response of a human cell to heat is the activation of a preexisting regulatory factor.
Mol Cell Biol 1987 Apr
PMID:Heat-inducible human factor that binds to a human hsp70 promoter. 360 Jun 34

Mouse somatic tissues contain low levels of transcripts homologous to the heat shock-inducible and cognate members of the heat shock protein 70 (hsp70) gene family. An abundant, unique sized hsp70 mRNA of 2.7 kilobases (kb) is present in testes in the absence of exogenous stress. Its expression is restricted to germ cells and is developmentally regulated. The 2.7-kb transcript first appears during the haploid phase of spermatogenesis and is stable throughout the morphogenic stages of spermiogenesis. A 2.7-kb hsp70 mRNA is present in rat and human testes. These observations suggest that a member of the hsp70 gene family plays a role in the development of the mammalian male germ cell lineage.
Mol Cell Biol 1987 May
PMID:Developmental-stage-specific expression of the hsp70 gene family during differentiation of the mammalian male germ line. 360 Jun 44

The gene encoding the human 70-kilodalton heat shock protein (HSP70) is subject to activation by the adenovirus E1A gene product and appears to be regulated in the absence of heat shock by a cellular activity similar to E1A. Given the relation of E1A to alteration of growth control, we have investigated the expression of the HSP70 gene during the cell cycle. Assay of mRNA levels after release from a thymidine-aphidicolin block revealed a 20-fold increase in mRNA abundance, reaching a peak level in the post-S-phase period. Upon reaching this peak level, the abundance of the mRNA then declined as the cells entered the next cycle. Control of the abundance of the mRNA during the cell cycle appeared to be primarily at the level of transcription as measured in nuclear runoff assays. Very similar results were obtained by analyzing the expression of the HSP70 gene in the adenovirus-transformed 293 cell line. Furthermore, the E1A gene was also found to be cell cycle regulated; the activation and peak level of the E1A mRNA occurred at an earlier time than those of the heat shock mRNA, consistent with, but not proof of, the hypothesis that E1A is responsible for the cell cycle control of the HSP70 expression. We therefore suggest that the E1A-like cellular activity may govern certain aspects of cell cycle transcription.
Mol Cell Biol 1985 Apr
PMID:Cell cycle control of the human HSP70 gene: implications for the role of a cellular E1A-like function. 387 94

Incubation of chicken reticulocytes at elevated temperatures (43 to 45 degrees C) resulted in a rapid change in the pattern of protein synthesis, characterized by the decreased synthesis of normal proteins, e.g., alpha and beta globin, and the preferential and increased synthesis of only one heat shock protein, HSP70. The repression of globin synthesis was not due to modifications of globin mRNA because the level of globin mRNA and its ability to be translated in vitro were unaffected. The HSP70 gene in reticulocytes was transcribed in non-heat-shocked cells, yet HSP70 was not efficiently translated until the cells had been heat shocked. In non-heat-shocked reticulocytes, HSP70 mRNA was a moderately abundant mRNA present at 1 to 2% of the level of globin mRNA. The rapid 20-fold increase in the synthesis of HSP70 after heat shock was not accompanied by a corresponding increase in the rate of transcription of the HSP70 gene or accumulation of HSP70 mRNA. These results suggest that the elevated synthesis of HSP70 is due to the preferential utilization of HSP70 mRNA in the heat-shocked reticulocyte. The heat shock-induced alterations in the reticulocyte protein-synthetic apparatus were not reversible. Upon return to control temperatures (37 degrees C), heat-shocked reticulocytes continued to synthesize HSP70 at elevated levels whereas globin synthesis continued to be repressed. Despite the presence of HSP70 mRNA in non-heat-shocked reticulocytes, we found that continued transcription was necessary for the preferential translation of HSP70 in heat-shocked cells. Preincubation of reticulocytes with the transcription inhibitor actinomycin D or 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole blocked the heat shock-induced synthesis of HSP70. Because the level of HSP70 mRNA was only slightly diminished in cells treated with actinomycin D, we suggest two possible mechanisms for the preferential translation of HSP70 mRNA: the translation of only newly transcribed HSP70 mRNA or the requirement of a newly transcribed RNA-containing factor.
Mol Cell Biol 1984 Nov
PMID:Heat shock-induced translational control of HSP70 and globin synthesis in chicken reticulocytes. 651 24


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>