UMLS:C0038187 - FACTA Search

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Query: UMLS:C0038187 (starvation)
24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The U2 small nuclear ribonucleoprotein particle (snRNP) auxiliary factor, U2AF, is an essential splicing factor required for recognition of the polypyrimidine tract and subsequent U2 snRNP assembly at the branch point. Because Caenorhabditis elegans introns lack both polypyrimidine tract and branch point consensus sequences but have a very highly conserved UUUUCAG/R consensus at their 3' splice sites, we hypothesized that U2AF might serve to recognize this sequence and thus promote intron recognition in C. elegans. Here we report the cloning of the gene for the large subunit of U2AF, uaf-1. Three classes of cDNA were identified. In the most abundant class the open reading frame is similar to that for the U2AF65 from mammals and flies. The remaining two classes result from an alternative splicing event in which an exon containing an in-frame stop codon is inserted near the beginning of the second RNA recognition motif. However, this alternative mRNA is apparently not translated. Interestingly, the inserted exon contains 10 matches to the 3' splice site consensus. To determine whether this feature is conserved, we sequenced uaf-1 from the related nematode Caenorhabditis briggsae. It is composed of six exons, including an alternatively spliced third exon interrupting the gene at the same location as in C. elegans. uaf-1 is contained in an operon with the rab-18 gene in both species. Although the alternative exons from the two species are not highly conserved and would not encode related polypeptides, the C. briggsae alternative exon has 18 matches to the 3' splice site consensus. We hypothesize that the array of 3' splice site-like sequences in the pre-mRNA and alternatively spliced exon may have a regulatory role. The alternatively spliced RNA accumulates at high levels following starvation, suggesting that this RNA may represent an adaption for reducing U2AF65 levels when pre-mRNA levels are low.
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PMID:Cloning of Caenorhabditis U2AF65: an alternatively spliced RNA containing a novel exon. 900 Dec 48

Genetic studies in animal models of microcytic anemia and biochemical studies of transport have implicated the Nramp2 gene in iron transport. Nramp2 generates two alternatively spliced mRNAs that differ at their 3' untranslated region by the presence or absence of an iron-response element (IRE) and that encode two proteins with distinct carboxy termini. Antisera raised against Nramp2 fusion proteins containing either the carboxy or amino termini of Nramp2 and that can help distinguish between the two Nramp2 protein isoforms (IRE: isoform I; non-IRE: isoform II) were generated. These antibodies were used to identify the cellular and subcellular localization of Nramp2 in normal tissues and to study possible regulation by dietary iron deprivation. Immunoblotting experiments with membrane fractions from intact organs show that Nramp2 is expressed at low levels throughout the small intestine and to a higher extent in kidney. Dietary iron starvation results in a dramatic upregulation of the Nramp2 isoform I in the proximal portion of the duodenum only, whereas expression in the rest of the small intestine and in kidney remains largely unchanged in response to the lack of dietary iron. In proximal duodenum, immunostaining studies of tissue sections show that Nramp2 protein expression is abundant under iron deplete condition and limited to the villi and is absent in the crypts. In the villi, staining is limited to the columnar absorptive epithelium of the mucosa (enterocytes), with no expression in mucus-secreting goblet cells or in the lamina propria. Nramp2 expression is strongest in the apical two thirds of the villi and is very intense at the brush border of the apical pole of the enterocytes, whereas the basolateral membrane of these cells is negative for Nramp2. These results strongly suggest that Nramp2 is indeed responsible for transferrin-independent iron uptake in the duodenum. These findings are discussed in the context of overall mechanisms of iron acquisition by the body.
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PMID:Cellular and subcellular localization of the Nramp2 iron transporter in the intestinal brush border and regulation by dietary iron. 1036 Nov 39

Neuronal differentiation involves Rac and Cdc42 GTPases. alpha-Chimaerin, a Rac/Cdc42 regulator, occurs as alpha1- and alternatively spliced Src homology 2 (SH2) domain-containing alpha2-isoforms. alpha2-chimaerin mRNA was highly expressed in the rat embryonic nervous system, especially in early postmitotic neurons. alpha1-chimaerin mRNA was undetectable before embryonic day 16.5. Adult alpha2-chimaerin mRNA was restricted to neurons within specific brain regions, with highest expression in the entorhinal cortex. alpha2-chimaerin protein localized to neuronal perikarya, dendrites, and axons. The overall pattern of alpha2-chimaerin mRNA expression resembles that of cyclin-dependent kinase regulator p35 (CDK5/p35) which participates in neuronal differentiation and with which chimaerin interacts. To determine whether alpha2-chimaerin may have a role in neuronal differentiation and the relevance of the SH2 domain, the morphological effects of both chimaerin isoforms were investigated in N1E-115 neuroblastoma cells. When plated on poly-lysine, transient alpha2-chimaerin but not alpha1-chimaerin transfectants formed neurites. Permanent alpha2-chimaerin transfectants generated neurites whether or not they were stimulated by serum starvation, and many cells were enlarged. Permanent alpha1-chimaerin transfectants displayed numerous microspikes and contained F-actin clusters, a Cdc42-phenotype, but generated few neurites. In neuroblastoma cells, alpha2-chimaerin was predominantly soluble with some being membrane-associated, whereas alpha1-chimaerin was absent from the cytosol, being membrane- and cytoskeleton-associated, paralleling their subcellular distribution in brain. Transient transfection with alpha2-chimaerin mutated in the SH2 domain (N94H) generated an alpha1-chimaerin-like phenotype, protein partitioned in the particulate fraction, and in NGF-stimulated pheochromocytoma cell line 12 (PC12) cells, neurite formation was inhibited. These results indicate a role for alpha2-chimaerin in morphological differentiation for which its SH2 domain is vital.
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PMID:alpha2-chimaerin, a Cdc42/Rac1 regulator, is selectively expressed in the rat embryonic nervous system and is involved in neuritogenesis in N1E-115 neuroblastoma cells. 1143 94

The peripheral myelin protein (PMP22) gene is highly expressed in peripheral Schwann cells and encodes an important constituent of the myelin sheath. It is also expressed at lower levels in other normal tissues in which the protein is supposed to be involved in cell growth regulation. We recently reported frequent amplification and overexpression of PMP22 in high-grade osteosarcoma. Here, we analyzed PMP22 expression in five osteosarcoma tumors and three osteosarcoma cell lines. In normal Schwann cells, transcription of PMP22 starts at three promoters, P1A, P1B, and P2, which results in the synthesis of three alternatively spliced transcripts that all code for the same protein. We found a comparable expression pattern in normal osteoblasts. However, promoter P1A-driven transcripts were absent in all investigated tumors and cell lines and, compared to normal osteoblasts, the P1B/P2 transcript ratio was found to be increased in two of three cases with PMP22 overexpression and decreased in all five cases without overexpression. In normal Schwann cells and in NIH3T3 cells, PMP22 expression increases upon serum starvation-induced growth arrest. In contrast to this, serum withdrawal caused a considerable decrease of PMP22 expression in the osteosarcoma cell lines. We conclude that the different PMP22 expression in osteosarcoma may result in alternative availability of the PMP22 protein during the cell cycle and aberrant regulation of cell growth control in osteosarcoma tumorigenesis.
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PMID:Characterization of PMP22 expression in osteosarcoma. 1526 28

We tested the effect of CRH and related peptides in a large panel of human skin cells for growth factor/cytokine activities. In skin cells CRH action is mediated by CRH-R1, a subject to posttranslational modification with expression of alternatively spliced isoforms. Activation of CRH-R1 induced generation of both cAMP and IP3 in the majority of epidermal and dermal cells (except for normal keratinocytes and one melanoma line), indicating cell type-dependent coupling to signal transduction pathways. Phenotypic effects on cell proliferation were however dependent on both cell type and nutrition conditions. Specifically, CRH stimulated dermal fibroblasts proliferation, by increasing transition from G1/0 to the S phase, while in keratinocytes CRH inhibited cell proliferation. In normal and immortalized melanocytes CRH effect showed dichotomy and thus, it inhibited melanocyte proliferation in serum-containing medium CRH through G2 arrest, while serum free media led instead to CRH enhanced DNA synthesis (through increased transition from G1/G0 to S phase and decreased subG1 signal, indicating DNA degradation). CRH also induced inhibition of early and late apoptosis in the same cells, demonstrated by analysis with the annexin V stains. Thus, CRH acts on epidermal melanocytes as a survival factor under the stress of starvation (anti-apoptotic) as well as inhibitor of growth factors induced cell proliferation. In conclusion, CRH and related peptides can couple CRH-R1 to any of diverse signal transduction pathways; they also regulate cell viability and proliferation in cell type and growth condition-dependent manners.
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PMID:CRH functions as a growth factor/cytokine in the skin. 1624 3

The levels of three alternatively spliced mRNAs from the Manduca sexta allatotropin (Manse-AT) gene were determined following physiological manipulations during the larval, pupal and adult stages; starvation of larvae, induction of pupal diapause and adult mating experience. The juvenile hormone biosynthetic activity of the corpora allata (CA) was also determined in starved larvae and in mated and unmated females. Starvation of early fifth instar larvae specifically increased the amount of one Manse-AT mRNA that is predicted to encode Manse-AT and two related peptides, Manse-ATL-I and -II. The normal rapid decrease in the activity of the CA in last instar larvae was not observed in starved insects which maintained a relatively high rate of JH biosynthesis for at least 3 days. Diapause induction resulted in a small increase in one Manse-AT mRNA, but levels were much lower compared to those observed in larvae or adults. During the first 4 days of adult life, Manse-AT mRNA levels were not changed as a result of mating. However, in mated females, the rate of JH biosynthesis gradually increased, in sharp contrast to the relatively low level of CA activity seen in virgin females. These observations suggest the elevated activity of the CA in mated females is not simply due to the increased level of Manse-AT mRNA.
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PMID:Effects of starvation and mating on corpora allata activity and allatotropin (Manse-AT) gene expression in Manduca sexta. 1648 12

The wild-type p53 gene has been widely implicated in the regulation of hypermethylated in cancer-1 (HIC-1) transcription, a master growth regulatory gene with multiple promoters and, consequently, multiple alternatively spliced transcripts. We investigated the role of p53 (wild type and mutant, both endogenous and exogenous) in modulating the various HIC-1 transcripts. We discovered a novel unspliced HIC-1 transcript, identified as "f" in leukocytes and in the human cell lines U87MG (wild-type p53), U373MG (mutant p53), MCF-7 (wild-type p53), HeLa (p53 degraded by HPV18-E6 oncoprotein), and Saos-2 (p53 null). This transcript is initiated from a new transcription start site and has an intervening stop codon that would result in a possibly truncated 22-amino-acid polypeptide. When U87MG (wild-type p53) and MCF-7 cells (wild-type p53) were exposed to adverse growth conditions of serum starvation or treated with the chemotherapeutic agent cisplatin, cells underwent apoptosis and cell cycle arrest accompanied by increase in p53 and HIC-1 transcript levels. Although the increase of the HIC-1-spliced transcripts followed the increase of p53, increase in f transcript coincided with declining p53 and HIC-1 transcript and protein levels. Moreover, the levels of HIC-1 f transcript were not induced by exogenously transfected wild-type p53 in p53-mutated U373MG and p53-null Saos-2 cells, unlike the spliced transcripts that code for full-length HIC-1 protein. These findings suggest a working model wherein the status of f transcript, which is not under direct transcriptional control of wild-type p53, may influence the level of HIC-1 protein in cancer cells.
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PMID:Identification and functional characterization of a novel unspliced transcript variant of HIC-1 in human cancer cells exposed to adverse growth conditions. 1707 68

longitudinals-lacking (lola) was identified in Drosophila as a gene encoding several alternatively spliced transcription factors involved in axon guidance. Here we report that lola also plays a critical role in programmed cell death in the ovary. lola mutant germline clones show a high percentage of egg chambers with nurse cell nuclei persisting past stage 13, indicating a block in developmental nurse cell death. Mutants also show a disruption in the induced programmed cell death that occurs during mid-oogenesis in response to starvation. Further characterization revealed that lola germline clones exhibit abnormal nuclear organization which becomes increasingly severe with age. Chromatin appears diffuse and fails to condense properly or undergo DNA fragmentation in dying nurse cells. Masses of nuclear material accumulate in the ovaries of older flies containing lola germline clones. We propose that lola is necessary for complete chromatin condensation which occurs during programmed cell death in the ovary. Alleles differed in the strength of their phenotypes but interestingly, the severity of their ovarian phenotypes was independent of the strength of their neuronal phenotypes, suggesting a differential requirement for individual lola isoforms in the ovary and nervous system.
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PMID:The axon guidance gene lola is required for programmed cell death in the Drosophila ovary. 1733 58

Glucocorticoids (GCs) increase hepatic phosphatidate phosphatase (PAP1) activity. This is important in enhancing the liver's capacity for storing fatty acids as triacylglycerols (TAGs) that can be used subsequently for beta-oxidation or VLDL secretion. PAP1 catalyzes the conversion of phosphatidate to diacylglycerol, a key substrate for TAG and phospholipid biosynthesis. PAP1 enzymes in liver include lipin-1A and -1B (alternatively spliced isoforms) and two distinct gene products, lipin-2 and lipin-3. We determined the mechanisms by which the composite PAP1 activity is regulated using rat and mouse hepatocytes. Levels of lipin-1A and -1B mRNA were increased by dexamethasone (dex; a synthetic GC), and this resulted in increased lipin-1 synthesis, protein levels, and PAP1 activity. The stimulatory effect of dex on lipin-1 expression was enhanced by glucagon or cAMP and antagonized by insulin. Lipin-2 and lipin-3 mRNA were not increased by dex/cAMP, indicating that increased PAP1 activity is attributable specifically to enhanced lipin-1 expression. This work provides the first evidence for the differential regulation of lipin activities. Selective lipin-1 expression explains the GC and cAMP effects on increased hepatic PAP1 activity, which occurs in hepatic steatosis during starvation, diabetes, stress, and ethanol consumption.
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PMID:Glucocorticoids and cyclic AMP selectively increase hepatic lipin-1 expression, and insulin acts antagonistically. 1824 16

Alanine aminotransferase (Alt) provides a molecular link between carbohydrate and amino acid metabolism. In the cell context, the predominant Alt isozyme is located in the cytosol. To gain insight into the transcriptional regulation of the cytosolic alt gene (calt), we cloned and characterized the calt promoter from gilthead sea bream (Sparus aurata). Transient transfection of sea bass larvae cells with deleted calt promoter constructs and electrophoretic mobility shift assays allowed us to identify p300 and c-Myb as new factors in the transcriptional regulation of calt expression. Transfection studies carried out with an acetylase-deficient mutant p300 (p300DY) revealed that the acetyltransferase activity of p300 is essential for the p300-mediated transcriptional activation of S. aurata calt. We had previously found up-regulation of liver cAlt2, an alternatively spliced isoform of calt, under gluconeogenic conditions and in streptozotocin (STZ)-treated S. aurata. Quantitative RT-PCR assays showed that increased p300 and c-Myb mRNA levels in the liver of starved S. aurata contribute to enhancing the transcription of cAlt2. Consistently, the administration of insulin decreased both p300 and c-Myb expression. The mRNA levels of p300 and c-Myb were also analyzed in the liver of STZ-induced diabetic S. aurata. Treatment with STZ increased the expression of p300, whereas it decreased c-Myb. Our findings suggest an involvement of p300 and c-Myb in up-regulation of cAlt2 in the liver of S. aurata under starvation. In addition, these results provide evidence for a role of p300 in diabetes.
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PMID:Transactivation of cytosolic alanine aminotransferase gene promoter by p300 and c-Myb. 2057 75

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