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)

Gln3p is a GATA-type transcription factor responsive to different nitrogen nutrients and starvation in yeast Saccharomyces cerevisiae. Recent evidence has linked TOR signaling to Gln3p. Rapamycin causes dephosphorylation and nuclear translocation of Gln3p, thereby activating nitrogen catabolite repressible-sensitive genes. However, a detailed mechanistic understanding of this process is lacking. In this study, we show that Tor1p physically interacts with Gln3p. An intact TOR kinase domain is essential for the phosphorylation of Gln3p, inhibition of Gln3p nuclear entry and repression of Gln3p-dependent transcription. In contrast, at least two distinct protein phosphatases, Pph3p and the Tap42p-dependent phosphatases, are involved in the activation of Gln3p. The yeast pro-prion protein Ure2p binds to both hyper- and hypo-phosphorylated Gln3p. In contrast to the free Gln3p, the Ure2p-bound Gln3p is signifcantly resistant to dephosphorylation. Taken together, these results reveal a tripartite regulatory mechanism by which the phosphorylation of Gln3p is regulated.
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PMID:Tripartite regulation of Gln3p by TOR, Ure2p, and phosphatases. 1094 Mar 1

The male accessory glands (MAGs) of Leptinotarsa decemlineata produce an 8kDa peptide, designated Led-MAGP, that is recognized by monoclonal antibody MAC-18. The site of synthesis, amino acid sequence and the gene encoding this peptide have been documented ([Smid and Schooneveld, 1992][Smid et al., 1997]). The primary structure is homologous to the N-terminal hexa-repeat section of the chicken prion protein ([Harris et al., 1991]). The biological function of the Led-MAGP has yet to be determined. For further research, large amounts of Led-MAGP is required, both for the production of a more specific antiserum, as well as for application in bio-assays. This paper describes the expression of Led-MAGP in insect cells infected with recombinant baculovirus, and the production of a polyclonal antibody against this recombinant peptide. The peptide was expressed under the control of the polyhedrin promotor. The resulting product was HPLC-purified, and analysis on Western blots immuno-labelled with MAC-18 confirmed that the correct peptide was produced. Purified recombinant peptide was also analyzed by Edman degradation and mass spectrometry; this indicated that it was N-terminally blocked and that the methionine residue at position 7 was oxidized. Large scale production resulted in the formation of aggregations of Led-MAGP, nevertheless a substantial proportion remained in a soluble state and could be harvested. A polyclonal antiserum encoded #87 was produced against recombinant Led-MAGP and its specificity was tested on Western blots of authentic peptide and on LM and EM sections of MAGs. All labelling results were equal to those obtained after MAC-18 labelling. However, antiserum #87 proved to be superior compared to MAC-18, since it recognizes the MAG peptide in normally fed, sexually active males, whereas MAC-18 labelling can only be accomplished after 7 days of starvation of the males. Therefore, the new antiserum #87 enables us to study the transfer dynamics of the Led-MAGP on histological sections.
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PMID:Expression of a male accessory gland peptide of Leptinotarsa decemlineata in insect cells infected with a recombinant baculovirus. 1276 59

Well known as detoxification enzymes, the glutathione transferases also function in prostaglandin and steroid hormone synthesis. New uses for the canonical glutathione transferase fold are becoming apparent; the bacterial stringent starvation protein SspA and the yeast prion protein Ure2p (both transcription factors) were found to adopt this fold, but their roles remain unclear. The intracellular chloride ion channel CLIC1 adopts the canonical glutathione transferase fold in its soluble form and appears to undergo radical structural modification as part of its membrane insertion process. The structures of rat and human mitochondrial glutathione transferases have been solved: they adopt a topology similar to that of bacterial disulfide bond isomerases, leading to the suggestion that they have evolved independently of the canonical enzymes. Recent structural studies of integral membrane glutathione S-transferases from microsomes have revealed common patterns of tertiary and quaternary structure.
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PMID:Glutathione transferases: new functions. 1626 69

Copper transporter 1 (CTR1), cellular prion protein (PrP(C)), natural resistance-associated macrophage protein 2 (NRAMP2) and ATP7A proteins control the cell absorption and efflux of copper (Cu) ions in nervous tissues upon physiological conditions. Little is known about their regulation under reduced Cu availability, a condition underlying the onset of diffused neurodegenerative disorders. In this study, rat neuron-like cells were exposed to Cu starvation for 48 h. The activation of Caspase-3 enzymes and the impairment of Cu,Zn superoxide dismutase (Cu,Zn SOD) activity depicted the initiation of a pro-apoptotic program, preliminary to the appearance of the morphological signs of apoptosis. The transcriptional response related to Cu transport proteins has been investigated. Notably, PrP(C) transcript and protein levels were consistently elevated upon Cu deficiency. The CTR1 protein amount was stable, despite a two-fold increase in the transcript amount, meaning the activation of post-translational regulatory mechanisms. NRAMP2 and ATP7A expressions were unvaried. The up-regulated PrP(C) has been demonstrated to enhance the cell Cu uptake ability by about 50% with respect to the basal transport, and so sustain the Cu delivery to the Cu,Zn SOD cuproenzymes. Conclusively, the study suggests a pivotal role for PrP(C) in the cell adaptation to Cu limitation through a direct activity of ion uptake. In this view, the PrP(C) accumulation observed in several cancer cell lines could be interpreted as a molecular marker of cell Cu deficiency and a potential target of therapeutic interventions against disorders caused by metal imbalances.
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PMID:Role of the cellular prion protein in the neuron adaptation strategy to copper deficiency. 2236 49

We recently documented the co-purification of members of the LIV-1 subfamily of ZIP (Zrt-, Irt-like Protein) zinc transporters (LZTs) with the cellular prion protein (PrP(C)) and, subsequently, established that the prion gene family descended from an ancestral LZT gene. Here, we begin to address whether the study of LZTs can shed light on the biology of prion proteins in health and disease. Starting from an observation of an abnormal LZT immunoreactive band in prion-infected mice, subsequent cell biological analyses uncovered a surprisingly coordinated biology of ZIP10 (an LZT member) and prion proteins that involves alterations to N-glycosylation and endoproteolysis in response to manipulations to the extracellular divalent cation milieu. Starving cells of manganese or zinc, but not copper, causes shedding of the N1 fragment of PrP(C) and of the ectodomain of ZIP10. For ZIP10, this posttranslational biology is influenced by an interaction between its PrP-like ectodomain and a conserved metal coordination site within its C-terminal multi-spanning transmembrane domain. The transition metal starvation-induced cleavage of ZIP10 can be differentiated by an immature N-glycosylation signature from a constitutive cleavage targeting the same site. Data from this work provide a first glimpse into a hitherto neglected molecular biology that ties PrP to its LZT cousins and suggest that manganese or zinc starvation may contribute to the etiology of prion disease in mice.
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PMID:LIV-1 ZIP ectodomain shedding in prion-infected mice resembles cellular response to transition metal starvation. 2268 93

The mechanisms of neuronal death in protein misfolding neurodegenerative diseases such as Alzheimer's, Parkinson's and prion diseases are poorly understood. We used a highly toxic misfolded prion protein (TPrP) model to understand neurotoxicity induced by prion protein misfolding. We show that abnormal autophagy activation and neuronal demise is due to severe, neuron-specific, nicotinamide adenine dinucleotide (NAD(+)) depletion. Toxic prion protein-exposed neuronal cells exhibit dramatic reductions of intracellular NAD(+) followed by decreased ATP production, and are completely rescued by treatment with NAD(+) or its precursor nicotinamide because of restoration of physiological NAD(+) levels. Toxic prion protein-induced NAD(+) depletion results from PARP1-independent excessive protein ADP-ribosylations. In vivo, toxic prion protein-induced degeneration of hippocampal neurons is prevented dose-dependently by intracerebral injection of NAD(+). Intranasal NAD(+) treatment of prion-infected sick mice significantly improves activity and delays motor impairment. Our study reveals NAD(+) starvation as a novel mechanism of autophagy activation and neurodegeneration induced by a misfolded amyloidogenic protein. We propose the development of NAD(+) replenishment strategies for neuroprotection in prion diseases and possibly other protein misfolding neurodegenerative diseases.
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PMID:Neuronal death induced by misfolded prion protein is due to NAD+ depletion and can be relieved in vitro and in vivo by NAD+ replenishment. 2567 60