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)

The regulation of protein synthesis was studied in KRC-7 cells (rat hepatoma) grown in complete medium, during serum starvation, and mitogen activation. Upon serum starvation, the cells lost almost completely p67 mRNA, p67 protein, and protein synthesis activity. After phorbol 12-myristate 13-acetate addition, the same serum-starved cells regained p67 mRNA, p67 protein, and protein synthesis activity. Also, the extracts from the serum-starved cells phosphorylated the eukaryotic initiation factor-2 (eIF-2) alpha-subunit. This eIF-2 alpha-subunit phosphorylation was not observed when the extracts from either the cells grown in complete medium or mitogen-activated cells were used (Gupta, S., Wu, S., Chatterjee, N., Ilan, J., Ilan, J., Osterman, J. C., and Gupta, N. K. (1995) Gene Expr. 5, 113-122). We now report the following. 1) The eIF-2 kinase activity was the same in the cells grown in complete medium, after serum starvation, and subsequent mitogen stimulation. However, the eIF-2 kinase in the cells grown in complete medium and also after mitogen activation of the serum-starved cells cannot phosphorylate eIF-2 alpha-subunit as these cells contain p67. After removal of endogenous p67 by p67 antibodies, the extracts from all these cells similarly phosphorylated exogenously added eIF-2. 2) None of the cell extracts showed p67 deglycosylase activity. 3) The p67 mRNA was synthesized in serum-starved cells by expression of a p67 cDNA. The appearance of p67 mRNA in the serum-starved cells was accompanied by the appearance of p67 protein. Also, the rates of protein synthesis in the serum-starved cells were restored nearly to the level observed in the confluent cells. The expression of p67 cDNA also significantly increased protein synthesis rates in the cells grown in complete medium and in mitogen-activated cells. These results show that the loss of protein synthesis activity in serum-starved cells was due to loss of p67 mRNA. The expressed p67 mRNA was stable in serum-starved cells. These results, therefore, suggest that the loss of p67 mRNA in serum-starved cells is due to loss of p67 transcription. The p67 transcription regulates translation.
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PMID:p67 transcription regulates translation in serum-starved and mitogen-activated KRC-7 cells. 913 27

Regulation of vaccinia viral infection was studied using three animal cell lines: KRC-7 (rat hepatoma), L929 (mouse fibroblast), and CV-1 (African green monkey kidney). KRC-7 is highly enriched in p67, a glycoprotein which protects eIF-2 alpha-subunit from phosphorylation by eIF-2 kinases. We report: (i) At 5 pfu per cell of the virus, KRC-7 is resistant to the virus. Other cells are sensitive. At 25 pfu per cell of the virus, KRC-7 is also sensitive to the virus. After productive viral infection, the cell extracts showed strong p67-DG activity and actively deglycosylated exogenous p67. After p67-deglycosylation, the cell extracts also phosphorylated eIF-2. (ii) The rate of synthesis of a major host protein (approximately 45 kDa) in infected L929 cells measured after 2 h of viral infection declined more than 50%. The rate declined thereafter. The rate of synthesis of host proteins in viral-resistant KRC-7 cells (infected with 5 pfu per cell of the virus) remained unchanged. The mechanism of resistance of KRC7 cells to vacinia virus at 5 pfu per cell of the virus was investigated. The p67 level in these cells was varied by growing the cells under different physiological conditions such as serum starvation and expression of p67-sense and p67-antisense DNA. At low p67 level in the cells, p67-DG is activated. This deglycosylates p67 and inactivates p67. This accompanies eIF-2 phosphorylation and shutoff of host protein synthesis. At high p67 level in the cells, activation of p67-DG is prevented. This prevents shut-off of host protein synthesis and viral growth.
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PMID:Viral infection. I. Regulation of protein synthesis during vaccinia viral infection of animal cells. 918 99

Phosphorylation of the alpha-subunit of eukaryotic initiation factor 2 is the major regulatory step in the initiation of protein synthesis in mammals. P67, a cellular glycoprotein, protects phosphorylation of eIF2alpha from kinases. Previously, we reported that the D6/2 mutant of p67 has higher levels of protection of eIF2alpha phosphorylation (POEP) activity. In this study, we report that the D6/2 mutant and its double mutants containing second-site alanine substitutions at the five conserved amino acid residues (D251, D262, H331, E364, and E459) show increased POEP activity in serum-starved rat tumor hepatoma cells. Serum-restoration to those cells did not abolish their increased POEP activity except the D6/2+H331A double mutant. The latter mutant shows slight inhibition of POEP activity during serum starvation and this inhibition increased significantly during serum restoration. KRC-7 cells constitutively expressing the D6/2 mutant showed slightly decreased levels of PKR phosphorylation and significantly low level of phosphorylation of ERKs 1 and 2. The D6/2 mutant also showed increased binding with eIF2alpha and eIF2gamma and almost similar binding with ERKs 1 and 2 as compared to wild type p67. Altogether, our data demonstrate that the increased binding of the D6/2 mutant with the subunits of eIF2 may be in part the cause for its high POEP activity.
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PMID:The binding between p67 and eukaryotic initiation factor 2 plays important roles in the protection of eIF2alpha from phosphorylation by kinases. 1684 28