“Pleiotypic Response”

Hershko, Avram; Mamont, Pierre S.; Shields, Robert L.; Tomkins, Gordon M.

doi:10.1038/newbio232206a0

Cited by 525 publications

(215 citation statements)

References 62 publications

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“…The results reported in this paper are reminiscent of the effects of a number of other conditions which regulate cell growth, such as serum or growth factor deprivation [23,[29][30][31], amino acid starvation [27,28,32,33] and growth of cells to confluence [34]. In all Vol.…”

Section: Regulation Of Protein Synthesis By Interferonsmentioning

confidence: 89%

“…237 of these cases protein synthesis is closely controlled, largely through mechanisms operating at the level of polypeptide chain initiation. Changes in protein degradation are less consistent since both decreased rates [23] and increases rates [30,35,36] have been observed in other systems where the growth of cells in culture is inhibited. It is clear that regulation of the rate of protein synthesis is a common mode of controlling the rate at which cells can grow and proliferate.…”

Section: Regulation Of Protein Synthesis By Interferonsmentioning

confidence: 90%

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Inhibition of cell proliferation by interferons. Relative contributions of changes in protein synthesis and breakdown to growth control of human lymphoblastoid cells

McNurlan¹,

Clemens²

1986

Biochemical Journal

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Treatment of the Daudi line of human lymphoblastoid cells with concentrations of human interferons within the physiological range progressively inhibits cell proliferation over 1-4 days. Rigorous measurement of the overall rate of protein synthesis during this period, using a concentration of [3H]phenylalanine sufficient to equalize the specific radioactivity of intracellular and extracellular precursor pools, shows that protein synthesis becomes progressively inhibited as the growth inhibition develops. There is a strong correlation between inhibition of amino acid incorporation and inhibition of cell proliferation. In contrast, we find no evidence for any increase in protein degradation rate under these conditions. These results suggest that interferon treatment of susceptible cells can inhibit protein synthesis even in the absence of virus infection and that this inhibition is of a sufficient magnitude to account for the anti-proliferative effect. INTRODUCTIONThe ability of interferons to inhibit viral replication in infected cells through effects on [4][5][6]. On the other hand,-inhibition of incorporation of labelled amino acids has been observed in some systems in which cell proliferation is inhibited [7][8][9]. The human lymphoblastoid Daudi cell line is extremely sensitive in exhibiting a marked suppression of growth when human interferons are added in culture [10][11][12]. We have investigated, using this system, the extent to which the changes in growth rate can be correlated with changes in protein synthesis. In order to do this it is necessary to quantify both processes rigorously. Such an approach also allows indirect estimates to be made of the rate of protein breakdown, and of the relative contributions of changes in synthesis versus breakdown to the inhibition of cell growth caused by interferon treatment.The rate of incorporation of a radioactive amino acid into protein reflects both the actual rate at which protein is synthesized and the specific radioactivity of the precursor which is being incorporated. If the values of the latter are different between two populations of cells then spurious conclusions can be drawn. In an attempt to overcome any such problems we have adapted procedures developed for measurement of protein synthesis rates in perfused organs [13] and in tissues of

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Section: Regulation Of Protein Synthesis By Interferonsmentioning

confidence: 89%

Section: Regulation Of Protein Synthesis By Interferonsmentioning

confidence: 90%

Inhibition of cell proliferation by interferons. Relative contributions of changes in protein synthesis and breakdown to growth control of human lymphoblastoid cells

McNurlan¹,

Clemens²

1986

Biochemical Journal

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“…Because the cells in these systems multiply in response to the serum, it is apparent that serum increases the rate of protein accumulation; in the absence of increased protein synthesis there must therefore be a decrease in the rate of protein degradation. In other systems, including 3T3!cells (9,28), both synthesis and degradation of proteins in serum-stimulated cells are so affected as to maximize the accumulation of protein, and in a third category there are cells in which only protein synthesis is affected by serum (29). Because protein accumulation must parallel DNA accumulation for balanced growth, both protein synthesis and degradation may be involved in regulating cell multiplication.…”

Section: Mg2+mentioning

confidence: 99%

Major intracellular cations and growth control: Correspondence among magnesium content, protein synthesis, and the onset of DNA synthesis in BALB/c3T3 cells

Rubin

Terasaki

Sanui

1979

Proc. Natl. Acad. Sci. U.S.A.

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“…All three components are required with ATP for proteolytic activity, but thus far only the heat-labile factor has been shown to interact directly with ATP. A universally observed aspect of intracellular protein degradation is the marked dependence on adequate levels of ATP (1,2) as shown by its almost total depression in the presence of a wide range of inhibitors of energy production. Only recently have there been reports of ATP-dependent proteolysis in cellfree extracts.…”

mentioning

confidence: 99%

Resolution of the ATP-dependent proteolytic system from reticulocytes: a component that interacts with ATP.

Hershko¹,

Ciechanover²,

Rose³

1979

Proc. Natl. Acad. Sci. U.S.A.

191

109

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The ATP-dependent proteolytic cell-free system from reticulocytes has been resolved into three components, each of which is absolutely required for acid solubilization of 125I-labeled bofine serum albumin radioactivity. In addition to the previously reported heat-stable polypeptide [Ciechanover, A., Hod, Y. & Hershko, A. (1978) separated from the heat-labile species by salt precipitation. All three components are required with ATP for proteolytic activity, but thus far only the heat-labile factor has been shown to interact directly with ATP. A universally observed aspect of intracellular protein degradation is the marked dependence on adequate levels of ATP (1, 2) as shown by its almost total depression in the presence of a wide range of inhibitors of energy production. Only recently have there been reports of ATP-dependent proteolysis in cellfree extracts. Goldberg and colleagues have found that ATP stimulates protein degradation in cell-free extracts of reticulocytes (3) and Escherichia coli (4), and Roberts et al. showed that the proteolytic cleavage of bacteriophage X repressor in vitro requires ATP (5). We have studied the role of ATP in the degradation of abnormal globin chains in intact reticulocytes and in their soluble extracts and have found that in both cases ATP is required at or before the initial cleavage of the complete polypeptide molecule (6).To gain insight into the mechanisms by which ATP participates in protein breakdown, purification and characterization of the responsible enzymes are required. We have reported (7) that ATP-dependent protease acting on labeled globin can be fractionated into a heat-stable protein that is not retained on DEAE-cellulose (fraction 1) and a crude fraction eluted with 0.5 M KC1. The active principle of fraction 1, now designated APF-1, is a heat-stable and relatively small (Mr ; 9000) polypeptide that has no proteolytic activity but restores ATP-dependent proteolysis when combined with fraction 11 (7). We report here the further resolution of fraction II into two complementary activities, and identify one of the components as capable of interacting directly with ATP.The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. §1734 solely to indicate this fact. 3107MATERIALS AND METHODS Fractionation of Reticulocyte Extracts. Soluble lysates were prepared from ATP-depleted rabbit reticulocytes and separated on DEAE-cellulose into fractions I and II as described (7), except that the column was washed with a solution containing 20 mM KC1, 1 mM dithiothreitol, and 3 mM potassium phosphate (pH 7.0) before the elution of fraction II. APF-1 was purified frim fraction I by heat treatment, ammonium sulfate precipitation, and gel filtration on a column of Sephadex G-75, as described (7).Fraction II was separated by ammonium sulfate fractionation to fractions TIA (0-38% saturation) and IIB (42-75% saturation). The precipitates were dissolved in a min...

show abstract

“Pleiotypic Response”

Cited by 525 publications

References 62 publications

Inhibition of cell proliferation by interferons. Relative contributions of changes in protein synthesis and breakdown to growth control of human lymphoblastoid cells

Inhibition of cell proliferation by interferons. Relative contributions of changes in protein synthesis and breakdown to growth control of human lymphoblastoid cells

Major intracellular cations and growth control: Correspondence among magnesium content, protein synthesis, and the onset of DNA synthesis in BALB/c3T3 cells

Resolution of the ATP-dependent proteolytic system from reticulocytes: a component that interacts with ATP.

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