Glutamine Starvation of Murine Leukaemia Virus-infected Cells Inhibits the Readthrough of the gag-pol Genes and Proteolytic Processing of the gag Polyprotein

Gloger, Israel; Panet, Amos

doi:10.1099/0022-1317-67-10-2207

Cited by 4 publications

(4 citation statements)

References 17 publications

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“…Starvation of M-MuLV infected cells for glutamine diminished specifically pol gene expression (Gloger and Panet, 1986) suggesting glutamine suppression of the gag UAG termination codon. This assumption was shown to be correct by direct amino acid sequencing of the junction between Gag and Pol (Yoshinaka et a/., 1985b).…”

Section: Introductionmentioning

confidence: 99%

cis acting RNA sequences control the gag-pol translation readthrough in murine leukemia virus

et al. 1991

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The pol gene of the Moloney murine leukemia virus (M-MuLV) is expressed as a Gag-Pol fusion protein through an in-frame suppression of the UAG termination codon located between the two genes. The role of nucleotide context in suppression was investigated, in a rabbit reticulocyte lysate translation system, using site-directed mutagenesis. The results indicate that the translational readthrough is mediated by at least 50 bases long RNA sequence located 3' to the gag UAG termination codon. Within this sequence a short purine-rich sequence adjacent to the amber codon, highly conserved among different retroviruses, appears essential for M-MuLV suppression. Two alternative putative stem and loop like RNA structures can be drawn at the gag-pol junction, one abutting the gag UAG codon, and the second downstream to it. None of these structures appears to be important to the suppression process.

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Section: Introductionmentioning

confidence: 99%

cis acting RNA sequences control the gag-pol translation readthrough in murine leukemia virus

et al. 1991

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“…Determination of the N-terminal amino acid sequence of the purified MuLV protease protein demonstrated that the UAG gag codon is read as glutamine in the protease, suggesting that suppression of the amber codon is mediated by a glutamine tRNA (33). Further evidence for the involvement of glutamine tRNA was provided by the finding that starvation of MuLV-infected cells for glutamine, but not for other essential amino acids such as tyrosine and leucine, inhibits synthesis of Pr200Y'9-P°and blocks proteolytic processing of Pr659'9 (8). Recently, Kuchino et al reported that MuLV-infected cells contain elevated levels of a minor glutamine tRNA which was able to suppress the UAG codon of tobacco mosaic virus RNA in vitro (20).…”

mentioning

confidence: 99%

Translational readthrough of the murine leukemia virus gag gene amber codon does not require virus-induced alteration of tRNA

Feng

Hatfield

Rein

et al. 1989

J Virol

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An in vitro system to assay translational readthrough of the UAG termination codon at the murine leukemia virus (MuLV) gag-pol junction was developed by using rabbit reticulocyte lysates programmed by SP6generated Moloney gIluLV gag-pol mRNA. Under conditions in which the suppressor activity of the lysate was dependent on addition of tRNA, it could be shown that readthrough synthesis was stimulated to approximately the same extent by equivalent amounts of tRNA from MuLV-infected and uninfected NIH 3T3 cells. Analysis of glutamine tRNA, which mediates suppression in vivo, showed that the level of glutamine acceptor activity and the chromatographic profile of glutamine isoacceptors were unchanged following virus infection. On the basis of these results, we conclude that the suppressor tRNA occurs normally within the tRNA population of uninfected cells and need not be induced in response to virus infection. The pol proteins of murine leukemia virus (MuLV) are positioned on the genetic map in ihe order 5'-proteasereverse transcriptase-IN (integration protein)-3' (3, 17, 19, 22, 33) and are made from a large 200-kilodalton (kDa) precursor polypeptide, Pr200gag-pol, which is cleaved at a

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“…Furthermore, glutamine is required for the in vitro production of the Moloney (Gloger et al, 1985;Gloger and Panet, 1986) and Rauscher (Roberts and McGregor, 1989) murine leukemia viruses; depletion in glutamine and asparagine is of therapeutic benefit in mice infected with the Rauscher and Friend leukemia viruses (Roberts and McGregor, 1991).…”

mentioning

confidence: 99%

“…human tumors; among these, N-(phosphonacety1)-L-aspartic acid (PALA) and L-2-amino-3-(N-hydroxy-N-nitrosamino) propionic acid (L-alanosine) have undergone phase-I and -11 trials in several centers in the USA (Ardalan and Singh, 1987;Morton et al, 1987). Furthermore, glutamine is required for the in vitro production of the Moloney (Gloger et al, 1985;Gloger and Panet, 1986) and Rauscher (Roberts and McGregor, 1989) murine leukemia viruses; depletion in glutamine and asparagine is of therapeutic benefit in mice infected with the Rauscher and Friend leukemia viruses (Roberts and McGregor, 1991).…”

mentioning

confidence: 99%

Therapeutic effects of D‐aspartic acid β‐hydroxamate (DAH) on friend erythroleukemia

Tournaire¹,

Malley²,

Hamedi-Sangsari³

et al. 1994

Intl Journal of Cancer

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D-aspartic acid beta-hydroxamate (DAH), an aspartic acid analogue, exerts anti-tumoral activity against murine leukemia L5178Y both in vitro and in vivo. We show here that DAH displays activity against Friend leukemia cells (FLC) in vitro: a concentration of 2 mM results in a total inhibition of cell growth. DAH is also active in vivo against Friend virus (FV-P)-induced erythroleukemia. Treatment with DAH, given for 95 days as a single daily i.p. injection to DBA/2 mice 3 days following FV-P inoculation, induced a marked increase of 212% in the mean survival time (MST) of treated animals. Since FV-P-induced erythroleukemia is characterized by the proliferation of mature erythroid precursors, we examined the effect of DAH treatment on erythroid colony-forming cells (CFU-E) and observed that the number of CFU-E per spleen was 30 times lower in DAH-treated mice than in the controls. To gain further insight into the early effects of DAH treatment on the early phase of Friend disease, we examined the effects of short DAH treatment on spleen size, hematocrit and viremia in FV-P-infected mice. DAH treatment initiated 3 days post infection (p.i.) inhibited splenomegaly, prevented virus-induced polycythemia, and reduced serum viremia. Late DAH treatment (18 days p.i.) induced regression of FVP-induced disease as evidenced by reduction of spleen weight.

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Glutamine Starvation of Murine Leukaemia Virus-infected Cells Inhibits the Readthrough of the gag-pol Genes and Proteolytic Processing of the gag Polyprotein

Cited by 4 publications

References 17 publications

cis acting RNA sequences control the gag-pol translation readthrough in murine leukemia virus

cis acting RNA sequences control the gag-pol translation readthrough in murine leukemia virus

Translational readthrough of the murine leukemia virus gag gene amber codon does not require virus-induced alteration of tRNA

Therapeutic effects of D‐aspartic acid β‐hydroxamate (DAH) on friend erythroleukemia

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