Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Protein kinase Cdelta (PKCdelta) is a member of the PKC family of phospholipid-dependent serine/threonine kinases and is involved in cell proliferation, apoptosis, and differentiation. Previous studies have suggested that different PKC isoforms might be translationally regulated. We report here that the 395-nt-long 5' untranslated region (5' UTR) of PKCdelta is predicted to form very stable secondary structures with free energies (deltaG values) of around -170 kcal/mol. The 5' UTR of PKCdelta can significantly repress luciferase translation in rabbit reticulocyte lysate but does not repress luciferase translation in a number of transiently transfected cell lines. By using a bicistronic luciferase reporter, we show that the 5' UTR of PKCdelta contains a functional internal ribosome entry segment (IRES). The activity of the PKCdelta IRES is greatest in densely growing cells and during apoptosis, when total protein synthesis and levels of full-length eukaryotic initiation factor 4G are reduced. However, the IRES activity of the 5' UTR of PKCdelta is not enhanced during serum starvation, another condition shown to inhibit cap-dependent translation, suggesting that its potency is dependent on specific cellular conditions. Accumulating data suggest that PKCdelta has a function as proliferating cells reach high density and in early and later events of apoptosis. Our studies suggest a mechanism whereby PKCdelta synthesis can be maintained under these conditions when cap-dependent translation is inhibited.
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PMID:The 5' untranslated region of protein kinase Cdelta directs translation by an internal ribosome entry segment that is most active in densely growing cells and during apoptosis. 1216 3

Activation of the angiotensin II type 1 receptor (AT1R) is closely involved in the pathogenesis of cardiovascular disease. The human AT1R (hAT1R) mRNA splice variants have long 5'-untranslated regions (5'-UTRs) ranging from 272 to 414 bp that have the potential to form stable secondary structures. In this study, we show that the 5'-UTR of hAT(1)R mRNAs contains an internal ribosome entry site (IRES) located within the first 40 bp of the proximal end of exon 1. Experiments utilizing the hAT1R 5'-UTR as a molecular decoy demonstrate a reduction in IRES activity of approximately 50%. This inhibition is most efficient for the hAT1R IRES suggesting that a defined set of trans-factors are required to initiate translation through this cis-element. Translation initiation from the hAT1R IRES appears to be physiologically relevant since IRES activity was maintained during serum starvation, a cellular stress known to inhibit cap-dependent translation. These results suggest that cap-independent translation initiation by internal ribosome entry may represent an important mechanism for the regulation of hAT1R expression.
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PMID:Translation of the human angiotensin II type 1 receptor mRNA is mediated by a highly efficient internal ribosome entry site. 1465 50

A putative glucose transporter, GLUT1, is reported for Atlantic cod Gadus morhua. A combination of RT-PCR, RLM-RACE and genome walking were used to articulate a 4560 bp cDNA (GenBank accession number AY526497). It contains a 149 bp 5' UTR, a 1470 bp open reading frame and a 2941 bp 3' UTR. At the nucleotide level, the cod GLUT1 ORF shares 78.2% sequence identity to human GLUT1 and the deduced amino acid sequence clusters with GLUT1s from rainbow trout and carp. GLUT1 transcript is highly expressed in brain, gill, heart and kidney and expressed to a lower level in at least six other tissues. Expression is evident immediately upon fertilization of eggs. Six hours of hypoxia at 40% DO(2) did not alter expression levels in brain, gill, heart or kidney. The level of expression is not substantially altered in heart during low temperature challenge, although there is a suggestion that colder temperature could lead to lower levels of expression, consistent with the concept that the cold-acclimated heart has a reduced dependence upon glucose as a metabolic fuel. Two months of starvation did not significantly alter the level of expression of GLUT1 in heart. This is in marked contrast to the rat heart where fasting leads to a substantial decrease in GLUT1 levels. Overall, there is a ubiquitous tissue distribution of GLUT1, consistent with other species, and the level of gene expression, especially in heart, is relatively constant over a range of physiological conditions.
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PMID:Sequence and expression of a constitutive, facilitated glucose transporter (GLUT1) in Atlantic cod Gadus morhua. 1557 63

A dramatic overexpression of IGFBP-1 is responsible for growth inhibition, in response to a low-protein diet feeding. It has been demonstrated that a fall in the amino acid concentration was directly responsible for IGFBP-1 induction. In this report, we sought to determine the mechanism by which amino acid limitation upregulates IGFBP-1 expression. Our results show that both transcriptional activation and mRNA stabilization are involved. We also demonstrate that (i) the mGCN2/ATF4 pathway is not involved in this regulation and (ii) the 3'UTR of IGFBP-1 mRNA is responsible for its destabilization and regulates its stability in response to amino acid starvation.
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PMID:Induction of IGFBP-1 expression by amino acid deprivation of HepG2 human hepatoma cells involves both a transcriptional activation and an mRNA stabilization due to its 3'UTR. 1586 98

The post-transcriptional control of mRNA levels is a very powerful mechanism which allows cells to quickly change the amount of specific proteins. In this study, we wanted to analyze whether the Brn-3b transcription factor, essential for the proper development of mouse retinal ganglion cells, is subjected to such post-transcriptional regulation. In particular, due to its conservation amongst different species, we wanted to study the role of its 3' untranslated region (3'UTR). We show that the 3'UTR of the Brn-3b mRNA does indeed contain regulatory sequences that mediate mRNA degradation upon serum starvation-induced differentiation of ND7 neuroblastoma cells. The specific region mediating this effect has been characterized and two different microRNAs that potentially regulate the stability of Brn-3b have been identified. Moreover we show that Dicer, one of the key enzymes in the production of microRNAs, is strongly up-regulated in ND7 cells subjected to differentiation.
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PMID:Post-transcriptional regulation of the Brn-3b transcription factor in differentiating neuroblastoma cells. 1749 Jun 55

RyhB is a small RNA (sRNA) that downregulates about 20 genes involved in iron metabolism. It is expressed under low iron conditions and pairs with specific mRNAs to trigger their rapid degradation by the RNA degradosome. In contrast to this, another study has suggested that RyhB also activates several genes by increasing their mRNA level. Among these activated genes is shiA, which encodes a permease of shikimate, an aromatic compound participating in the biosynthesis of siderophores. Here, we demonstrate in vivo and in vitro that RyhB directly pairs at the 5'-untranslated region (5'-UTR) of the shiA mRNA to disrupt an intrinsic inhibitory structure that sequesters the ribosome-binding site (Shine-Dalgarno) and the first translation codon. This is the first demonstration of direct gene activation by RyhB, which has been exclusively described in degradation of mRNAs. Our physiological results indicate that the transported compound of the ShiA permease, shikimate, is important under conditions of RyhB expression, that is, iron starvation. This is demonstrated by growth assays in which shikimate or the siderophore enterochelin correct the growth defect observed for a ryhB mutant in iron-limited media.
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PMID:The small RNA RyhB activates the translation of shiA mRNA encoding a permease of shikimate, a compound involved in siderophore synthesis. 1754 19

We have identified previously a destabilizing adenine- and uracil-rich element (ARE) in the 3'-UTR of bcl-2 mRNA that interacted with ARE-binding proteins to down-regulate bcl-2 gene expression in response to apoptotic stimuli. We have also described three contiguous 2'-O-methyl oligoribonucleotides (ORNs) in both sense and antisense orientation with respect to the bcl-2 ARE that are able to regulate the bcl-2 mRNA half-life and Bcl-2 protein level in two different cell lines. Here we show that treatment of neuronal cell line (SHSY-5Y) with antisense ORNs targeting the bcl-2 ARE (bcl-2 ARE asORNs) prevents bcl-2 down-regulation in response to apoptotic stimuli with glucose/growth factor starvation (Locke medium) or oxygen deprivation and enhances the apoptotic threshold as evaluated by time-lapse videomicroscopy, fluorescence-activated cell sorting analysis, and caspase-3 activation. Additional effects of bcl-2 ARE asORNs included inhibition of cell cycle entry and a marked increase of cellular neurite number and length, a hallmark of neuronal differentiation resulting from bcl-2 up-regulation. The ability of bcl-2 ARE asORNs to enhance the apoptotic threshold and to induce neuronal differentiation implies their potential application as a novel informational tool to protect cells from ischemic damage and to prevent neuronal degeneration.
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PMID:Impact of targeting the adenine- and uracil-rich element of bcl-2 mRNA with oligoribonucleotides on apoptosis, cell cycle, and neuronal differentiation in SHSY-5Y cells. 1798 53

Malic enzyme catalyzes decarboxylation of malate to pyruvate and CO(2), providing de novo biosynthesis of fatty acids with NADPH. Since lipogenesis in ruminants, contrarily to some monogastric species like human and rodents, occurs predominantly in adipose tissue, the activity of many lipogenic enzymes is higher in adipose tissue compared to liver. Expression of malic enzyme is regulated by nutrition; refeeding after a period of starvation results to an induction of the enzyme. Here we present the nucleotide sequence of two transcripts of the ovine cytosolic malic enzyme gene that differ at the length of the 3' UTR. These are the first published cDNA sequences for ruminant species and share high similarity with the corresponding sequences of other species. Malic enzyme mRNA was present in every ovine tissue that was examined. In agreement with the fact that adipose tissue is the major lipogenic site for ruminants, mRNA levels in adipose tissue were higher than in liver. Refeeding after two weeks of caloric restriction resulted in a two-fold increase of the mRNA level of malic enzyme in adipose tissue.
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PMID:Molecular cloning and characterization of the sheep malic enzyme cDNA. 1867 27

Regulation of mRNA decay is an important step modulating gene expression. The stability of numerous eukaryotic mRNAs is controlled by adenosine/uridine-rich elements (AREs) located in their 3'UTR. In Saccharomyces cerevisiae, the Cth2 protein stimulates the decay of target ARE mRNAs on iron starvation. Cth2, and its mammalian homologue tristetraprolin, contains a characteristic tandem CCCH zinc-finger essential for ARE binding and mRNA decay. We have performed a structure-function analysis of Cth2 to understand the mechanism(s) by which it destabilizes mRNAs. This indicated that a conserved N-terminal region of Cth2 is essential for its decay function but dispensable for RNA binding. Unexpectedly, Cth2 mutants lacking this domain blocked the normal 3' end processing of ARE mRNAs leading to the formation of extended transcripts. These can also be detected in mutant of the polyadenylation machinery. Consistently, Cth2 localization in the nucleus suggests that it may interfere with poly(A) site selection. Our analysis reveal that ARE-binding protein may affect mRNA 3' end processing and that this contributes to mRNA destabilization.
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PMID:Regulation of ARE transcript 3' end processing by the yeast Cth2 mRNA decay factor. 1892 25

The high-affinity phosphate transporter AtPht1;4 (Arabidopsis phosphate transporter1;4) is not only induced in response to inorganic phosphate (Pi) starvation but also preferentially expressed in the roots of Arabidopsis. In this study, we carried out AtPht1;4 promoter deletion analysis to identify regions that control the Pi responsiveness and spatiotemporal expression of the gene. Expression cassettes with truncated promoter fragments cloned to GUS (beta-glucuronidase) coding sequence were developed. Full-length promoter (-2327) and truncations up to -1436 (from the translational start) showed normal expression of GUS in various parts of the plants. The Pi responsiveness and inducibility of the reporter gene remained unaltered. However, deletion of the promoter region containing the first PHR1-binding site (P1BS) motif (-1350) abolished the AtPht1;4 expression in roots but not in aerial parts. A 164-bp region immediately upstream of the transcription start site appears to be sufficient for the basal expression of the gene. Interestingly, the 5'UTR (5' untranslated region) intron exhibited weak promoter activity as evidenced by its ability to drive the expression of AtPht1;4 in stipules and reproductive organs. Further analyses showed that the 5'UTR intron is essential for AtPht1;4 expression in root tips besides enhancing the level of expression in roots during Pi starvation. However, expression of AtPht1;4 in aerial parts of the plant was not influenced by the intron. Together these results suggest that expression of AtPht1;4 in the roots and aerial parts is regulated by independent mechanisms.
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PMID:Promoter deletion analysis elucidates the role of cis elements and 5'UTR intron in spatiotemporal regulation of AtPht1;4 expression in Arabidopsis. 1950 64


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