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PubMed1989

In situ hybridization detection of marked differences in pre-proopiomelanocortin messenger ribonucleic acid content of individual corticotropes and melanotropes.

Recently, heterogeneity of POMC mRNA content between intermediate lobe melanotropes of the rat pituitary gland was demonstrated by in situ hybridization of tissue sections. In the present study the heterogeneity of POMC mRNA content in dispersed rat pituitary cells has been investigated. Acutely dispersed cells from adult male rat anterior or neurointermediate lobe tissues were adhered to poly-L-lysine-coated coverslips. The cells were fixed and then hybridized with 35S-labeled POMC or 1B15 (cyclophilin) cRNA. Parallel studies measuring constitutively expressed cellular 1B15 mRNA content were undertaken to ensure that the apparent single cell differences in POMC mRNA were not inherent to the in situ hybridization procedure. When classified by image analysis, extensive differences in silver grain densities were seen over POMC mRNA-containing cells from both lobes. To determine if mRNA in polysomal configurations was less accessable for hybridization with probes than naked mRNA, cells were preincubated with pactamycin, a potent inhibitor of ribosomal initiation of protein synthesis. Pactamycin had no effect on these results. Thus, there appears to be large differences in POMC mRNA content between individual pituitary cells expressing the same gene product.

Adrenocorticotropic Hormone↗
PubMed1975

Inhibition of epidermal DNA synthesis by cycloheximide and other inhibitors of protein synthesis.

Cycloheximide, pactamycin and tenuazonic acid inhibit protein synthesis in eukaryotic cells. It is the purpose of these studies to determine whether these agents would be effective in vivo inhibitors of epidermal DNA synthesis. Single I.P. administration of 1.5 mg/kg cycloheximide, 0, 1 or 3 hours prior to a 45 minute pulse of thymidine-3H inhibited epidermal DNA synthesis by 68%, 63% and 88%, respectively. This response was dose related at 3.75 hours after cycloheximide with no effect at 0.375 mg/kg and maximal inhibition at 1.5 mg/kg. Epidermal DNA synthesis was inhibited 18, 29 and 62% at doses of 1.5, 3.0 and 6.0 mg/kg pactamycin administered 3 hours before thymidine-3H. Similarly, at doses of 70 and 140 mg/kg tenuazonic acid, epidermal DNA synthesis was inhibited by 50% and 60%, respectively. These data suggest the possible use of protein synthesis inhibitors in epidermal disorders.

Animals↗
PubMed1984

Ia-restricted interaction of normal lymphoid cells and SJL lymphoma (reticulum cell sarcoma) leading to lymphokine production. III. Relative roles of reticulum cell sarcoma and normal lymphoid cells in lymphokine production.

Production of interleukin 2 (IL-2) in mixed lymphocyte cultures of SJL/J lymph node (LN) and gamma-irradiated, syngeneic lymphoma cells of transplantable reticulum cell sarcoma (gamma-RCS) was abolished by pactamycin pretreatment of gamma-RCS. LN cells needed for this interaction were Lyt-2 T-cells, not adherent to Sephadex G-10. The effect of separation of T-cells and gamma-RCS after the first 24 hours of culture suggested that both components contributed to the IL-2 production. Exogenous IL-2, but not interleukin 1 (IL-1), restored the ability of pactamycin-treated gamma-RCS to induce syngeneic T-cell proliferation. The inability of T-cells from "nonresponder" F1 hybrids of SJL to proliferate to gamma-RCS was not corrected by addition of IL-1 or IL-2. Interferon (IFN) production also required the presence of untreated gamma-RCS and LN cells, but it was dependent on a Sephadex G-10 and plastic adherent cell in LN. IFN-free supernatant of LN cells plus gamma-RCS induced IFN production in fresh normal lymphoid cells, suggesting a possible indirect induction of this lymphokine. In addition, unirradiated RCS cells (la+ cells) produced immune IFN over a period of 3 weeks in vitro, after which the cells lost their viability. Prolonged IL-2 production was not observed in these cultures. The possible biological importance of the lymphokine production during the exaggerated syngeneic mixed lymphocyte reactions induced by RCS cells is discussed.

Animals↗
PubMed1982

Regulation of tyrosine aminotransferase messenger ribonucleic acid in rat liver. effect of cycloheximide on messenger ribonucleic acid turnover.

Tyrosine aminotransferase messenger ribonucleic acid (mRNA) activity in rat liver was rapidly increased 3-6-fold following in vivo administration of hydrocortisone acetate, dibutyryladenosine cyclic 3',5'-phosphate, or the protein synthesis inhibitor cycloheximide. Treatment with the steroid hormone or cyclic nucleotide in combination with cycloheximide resulted in levels of tyrosine aminotransferase mRNA 10-20-fold greater than control values. These changes in mRNA activity were not accompanied by changes in albumin mRNA or total liver template activity. The rapid decline in tyrosine aminotransferase mRNA activity following cordycepin inhibition of de novo RNA synthesis was prevented by cycloheximide treatment. This protection was not observed when pactamycin was substituted for cycloheximide, demonstrating that the inhibition of protein synthesis per se was not responsible for the stabilization of tyrosine aminotransferase mRNA. Based upon the effects of cycloheximide and pactamycin on rat liver polysome structure, it is concluded that the cycloheximide-mediated increase in tyrosine aminotransferase mRNA activity is the result of stabilization of the mRNA molecule which renders the message less susceptible to inactivation and degradation in the cytoplasm. The action of cycloheximide is very specific for tyrosine aminotransferase, phosphoenolpyruvate carboxykinase, and probably several other mRNAs that code for minor liver proteins that turn over rapidly in response to hormonal or metabolic stimuli.

Animals↗
PubMed2002

The permeability of the endoplasmic reticulum is dynamically coupled to protein synthesis.

Proteins synthesized by the rough endoplasmic reticulum (RER) co-translationally cross the membrane through the pore of a ribosome-bound translocon (RBT) complex. Although this pore is also permeable to small molecules, it is generally thought that barriers to their permeation prevent the cyclical process of protein translation from affecting the permeability of the RER. We tested this hypothesis by culturing Chinese hamster ovary-S cells with inhibitors of protein translation that affect the occupancy of RBTs by nascent proteins and then permeabilizing the plasma membrane and measuring the permeability of the RER to a small molecule, 4-methyl-umbelliferyl-alpha-d-glucopyranoside (4-MalphaG). The premature or normal release of nascent proteins by puromycin or pactamycin, respectively, increased the permeability of the RER to 4-MalphaG by 20-30%. In contrast, inhibition of elongation and the release of nascent proteins by cycloheximide did not increase the permeability, but it prevented the increase in permeability by pactamycin. We conclude that the permeability of the RER is coupled to protein translation by a simple gating mechanism whereby a nascent protein blocks the pore of a RBT during translation, but after release of the nascent protein the pore is permeable to small molecules as long as an empty ribosome remains bound to the translocon.

Animals↗
PubMed1972

Enhanced toxicity for mice of vincristine and other chemotherapeutic agents with Salmonella typhosa endotoxin and Pseudomonas aeruginosa.

The toxicity of Salmonella typhosa 0901 W endotoxin for BALB/c mice was potentiated by the administration of 375 mg of cyclophosphamide per kg, 16 mg of daunomycin per kg, 80 mg of methotrexate per kg, 8 mg of pactamycin per kg, 20 mg of polyinosinic-polycytidylic acid per kg, 1,000 mg of procarbazine per kg, and 1 or 4 mg of vincristine per kg. l-Asparaginase (20,000 units per kg) failed to potentiate endotoxin. Sedation following administration of 45 mg of pentobarbital per kg was prolonged in mice that had received 20,000 units of l-asparaginase per kg, 4 mg of daunomycin per kg, 120 mg of methotrexate per kg, 8 mg of pactamycin per kg, 10 mg of polyinosinic-polycytidylic acid per kg, 500 mg of procarbazine per kg, 2 mg of vincristine per kg, 2 mg of endotoxin per kg, or multiple doses of endotoxin. Mice pretreated with multiple endotoxin doses experienced a significant reduction in their lethal responses due to vincristine-endotoxin combinations; however, endotoxin-pretreated mice were more susceptible to vincristine alone than were normal mice. Simultaneous administration of 1 or 2 mg of vincristine per kg and 1 mg of endotoxin per kg produced greater lethality than sequential regimens. Pretreatment of mice with 65 mg of phenobarbital per kg on 4 consecutive days protected against vincristine-endotoxin combinations. Liver homogenates prepared from mice exposed previously to vincristine were capable of inactivating endotoxin. Vincristine lethality was increased by simultaneous administration of heat-killed cells of Pseudomonas aeruginosa isolated from mouse feces.

Animals↗
PubMed1980

Location of the initiation site for protein synthesis on foot-and-mouth disease virus RNA by in vitro translation of defined fragments of the RNA.

An mRNA-dependent reticulocyte lysate has been used to translate foot-and-mouth disease virus RNA in vitro. Polypeptides P16, P20a, and P88, which have been shown to be derived from the 5' end of the RNA by pactamycin mapping experiments with infected cells, were preferentially synthesized in vitro. Removal of VPg, the small protein covalently linked to the 5' end of the genome RNA, had no effect on the translation of the RNA. The two RNA fragments (L and S) produced by specific digestion of the polycytidylic acid [poly(C)] tract with RNase H were also translated in vitro. The L fragment, consisting of RNA to the 3' side of the poly(C) tract and including the polyadenylic acid [poly(A)] tract, directed the synthesis of the same products as those made by full-length RNA. However, no small defined products were produced when the S fragment, which contains the 5' end of the RNA, was translated. These results show that the major initiation site for protein synthesis on foot-and-mouth disease virus RNA is to the 3' side of the poly(C) tract. Furthermore, the use of N-formyl [35S]methionine tRNAfMet as a label for the initiation peptides showed that the major polypeptide labeled in lysates primed with both full-length RNA and the L fragment was P16, i.e., the protein nearest the initiation site for translation as deduced from pactamycin mapping experiments. Fragments of RNA were also translated in vitro. Those containing the poly(C) tract gave products similar to those produced when full-length RNA was translated. The polypeptides synthesized when fragments containing the poly(A) tract were used, however, did not resemble those made from full-length RNA.

Aphthovirus↗
PubMed1994

Induction of secretogranin II mRNA by protein synthesis inhibitors in GH4C1 cells.

The effect of cycloheximide (CHX) on the expression of secretogranin II (SgII), a member of the granin family of secretory proteins, was investigated in rat pituitary GH4C1 (GH) cells. The administration of CHX resulted in a dose- and time-dependent increase in SgII mRNA expression, the greatest effect (3.8-fold above control) being achieved with 1 microgram/ml CHX, which resulted in > 90% inhibition of protein synthesis. Emetine (1 microgram/ml), pactamycin (0.6 microgram/ml), anisomycin (2.5 micrograms/ml), and puromycin (100 micrograms/ml), protein synthesis inhibitors structurally and mechanistically unrelated to CHX, also increased the level of SgII mRNA expression. Treatment with forskolin (10 microM) alone had no effect on SgII mRNA levels but potentiated the effect of CHX. Neither 100 nM phorbol 12-myristate 13-acetate nor 45 mM KCl affected SgII mRNA levels in the absence or presence of 1 microgram/ml CHX. The effect of CHX was blocked by the transcription inhibitors actinomycin D (5 micrograms/ml) and 5,6-dichlorobenzimidazole riboside (20 micrograms/ml) but not by the coadministration of the polysome destabilizer pactamycin (0.6 microgram/ml), suggesting that the effect of CHX was transcriptional. These studies show that the expression of SgII mRNA is induced by protein synthesis inhibitors in GH cells, suggesting the presence of a labile repressor, which not only controls the basal expression of the SgII gene but also completely inhibits the stimulatory effect of forskolin.

Animals↗
PubMed1984

Analysis of antigen uptake and presentation by Epstein-Barr virus-transformed human lymphoblastoid B cells.

Epstein-Barr virus-transformed human B cells (EBV-B cells), but not resting B cells or B cells activated by T cell-derived factors, have been shown to support the proliferation of tetanus toxoid (TT)-specific autologous T cell clones in response to TT antigen. The accessory cell function of EBV-B cells was compared to that of monocytes with regard to antigen uptake and processing. After an 18-h incubation period with 125I-labeled TT, the amount of radioactivity associated with the cells (approximately 50 ng/10(7) cells) and the percentage of cells containing radiolabeled material (approximately 50%) were equivalent for EBV-B cells and monocytes. Like with monocytes, EBV-B cells pulsed with TT for 18 h or more were equivalent in their capacity to induce T cell proliferation to EBV-B cells to which soluble TT was added for the duration of the culture period. The requirements for antigen uptake and presentation to T cells were similar for both EBV-B cells and monocytes. Both processes were energy dependent, inhibited by cold (4 degrees C), 2-deoxyglucose, and azide, and both required no de novo protein synthesis as they were not affected by pretreatment of the cells with the irreversible protein inhibitor pactamycin . Trypsin treatment of antigen-pulsed EBV-B cells and monocytes followed by fixation for 1 min in 0.03% paraformaldehyde completely abolished the capacity of both cell types to induce T cell proliferation. In both EBV-B cells and monocytes, antigen presentation, but not antigen uptake, was inhibited by the addition of the lysosomotropic agent chloroquine during the antigen-pulse period suggesting that the mechanisms of antigen processing are similar for both cell types. Vacuoles positive for acid phosphatase with an electron microscopic structure similar to that of lysosomes were found in EBV-B cells but not in resting B cells or B cells activated by T cell-derived factors. The present observations indicate that EBV-B cells take up antigen and process it in a fashion similar to monocytes. The presence of lysosomes appears to correlate with the capacity of B cells to present antigen.

Azides↗
PubMed1985

Transcription of ribosomal RNA is differentially controlled in resting and growing BALB/c 3T3 cells.

Shortly after serum-deprived BALB/c 3T3 fibroblasts are stimulated to grow in medium containing 10% calf serum, the RNA polymerase I activity in permeabilized cells shows a two-fold increase over the values observed in either serum-deprived or density-inhibited resting cells. Inhibition of protein synthesis by pactamycin or cycloheximide specifically reduces the enhanced RNA polymerase I activity in serum-stimulated cultures without affecting the values in resting cells. On the other hand, inhibition of rRNA processing by the nucleoside analogs 5-fluoruridine and toyocamycin decreases the rate of 45S rRNA transcription in serum-stimulated cells but has no effect on the values found in resting cultures. These data suggest that the regulation of rRNA transcription occurs by two different mechanisms, depending on the growth state of the cell. One mechanism, in serum-stimulated cells, is dependent on a continuous protein synthesis and a correct 45S rRNA processing; the other, in resting cells, is independent of these two parameters.

Adenosine↗
PubMed1992

Inhibitors of protein synthesis cause increased hexose transport in cultured human fibroblasts by a mechanism other than transporter translocation.

We have investigated the effect of various inhibitors of protein synthesis on hexose transport in human skin fibroblasts using 2-deoxy-D-glucose (2-DG) and 3-0-methyl-D-glucose (3-OMG) to measure hexose transport. Exposure of glucose-fed, serum-free cultures to cycloheximide (CHX) (50 micrograms/ml) for 6 h resulted in increased 2-DG transport (3.81 +/- .53 vs. 6.62 +/- .88 nmoles/mg protein/2 min; n = 9) and 3-OMG transport (1.36 +/- .66 vs. 3.18 +/- .83 nmoles/mg protein/30 sec; n = 4) in the CHX exposed group. Under these conditions inhibition of protein synthesis was greater than 90%. This CHX induced transport increase was time dependent (approaching maximum within 1 h of exposure to CHX) and related to an increase in the Vmax of hexose transport in the CHX exposed group (18.4 +/- 2.4 vs. 4.8 +/- 1.1 nmoles 2-DG/mg protein/min) with no difference in the transport Km (1.55 +/- .63 vs. 2.92 +/- .59 mM). Further, the CHX induced increase in hexose transport was reversible. Exposure of human fibroblasts to inhibitors of protein synthesis with different mechanisms of action (e.g., puromycin, pactamycin, or CHX) all generated hexose transport increases in a concentration-dependent fashion correlating with their increasing inhibitory effects on protein synthesis. Nucleotidase enriched (i.e., plasma membrane) fractions of control and CHX-exposed cells showed no differences in D-glucose inhibitable cytochalasin B binding activity. Further, quantitative Western analysis of nucleotidase enriched fractions indicated CHX exposure resulted in no significant increase in glucose transporter mass compared with control plasma membrane fractions. Glucose deprived cells, however, which exhibited increased sugar transport comparable to the CHX-exposed group, did show increased glucose transporter mass in the plasma membrane fraction. The data indicate that inhibitors of protein synthesis can cause a significant elevation in hexose transport and that the hexose transporter mass in the isolated plasma membrane fractions did not reflect the whole cell transport change. It is suggested that a mechanism other than glucose transporter translocation to the plasma membrane may be involved in causing this sugar transport increase.

3-O-Methylglucose↗
PubMed1996

Type 1 phosphatase inhibitors reduce the restoration of guanine nucleotide exchange activity of eukaryotic initiation factor 2B inhibited reticulocyte lysates rescued by hemin.

In heme-deficient reticulocyte lysates, the alpha-subunit of eukaryotic initiation factor-2 (eIF-2alpha) is phosphorylated due to the activation of the heme-regulated eIF-2alpha kinase (HRI). Phosphorylation of eIF-2alpha impairs the guanine nucleotide exchange activity of eIF-2B and thereby inhibits or shuts off protein synthesis. Delayed addition of hemin to shut-off lysates inhibits the eIF-2alpha kinase activity of HRI and restores protein synthesis; under those conditions, the endogenous phosphatase of the lysate dephosphorylates phosphorylated eIF-2alpha and restores eIF-2B activity. In this report we present evidence that the restoration of eIF-2B activity is dependent on the concentration of added hemin and is related to HRI activity in lysates. The recovery of eIF-2B activity is not affected by protein synthesis inhibitors such as cycloheximide, pactamycin and puromycin, which do not affect the eIF-2alpha phosphorylation. Also, the functional eIF-2B activity that is available in hemin-supplemented lysates is not affected by phosphatase inhibitors such as okadaic acid and heat-stable inhibitor-2. However, the recovery of eIF-2B activity that is observed by the delayed addition of hemin to inhibited heme-deficient lysates is reduced by inhibitor-2 and high concentrations of okadaic acid. These findings suggest that a type 1 phosphatase is involved in the recovery of eIF-2B activity and protein synthesis upon delayed addition of hemin to heme-deficient lysates.

Animals↗
PubMed1993

Reversible phosphorylation of eukaryotic initiation factor 2 alpha in response to endoplasmic reticular signaling.

Agents, such as EGTA, thapsigargin, and ionophore A23187, that mobilize sequestered Ca2+ from the endoplasmic reticulum (ER) or dithiothreitol (DTT) that compromises the oxidizing environment of the organelle, disrupt early protein processing and inhibit translational initiation. Increased phosphorylation of eIF-2 alpha (5-fold) and inhibition of eIF-2B activity (50%) occur in intact GH3 cells exposed to these agents for 15 min (Prostko et al. J. Biol. Chem. 267:16751-16754, 1992). Alterations in eIF-2 alpha phosphorylation and translational activity in response to EGTA were reversed by addition of Ca2+ in excess of chelator while responses to DTT were reversible by washing. Exposure for 3 h to either A23187 or DTT, previously shown to induce transcription-dependent translational recovery, resulted in dephosphorylation of eIF-2 alpha in a manner blocked by actinomycin D. Phosphorylation of eIF-2 alpha in response to A23187 or DTT was not prevented by conventional inhibitors of translation including cycloheximide, pactamycin, puromycin, or verrucarin. Prolonged inhibition of protein synthesis to deplete the ER of substrates for protein processing resulted in increased eIF-2 alpha phosphorylation, decreased eIF-2B activity, and reduced monosome content that were indicative of time-dependent blockade; these inhibitors did not abolish polysomal content. Superphosphorylation of eIF-2 alpha occurred upon exposure of these preparations to either A23187 or DTT. Tunicamycin, an inhibitor of co-translational transfer of core oligosaccharide, provoked rapid phosphorylation of eIF-2 alpha and inhibition of translational initiation whereas sugar analog inhibitors of glycoprotein processing did neither. A flow of processible protein to the ER does not appear to be required for the phosphorylation of eIF-2 alpha in response to ER perturbants. We hypothesize that perturbation of the translocon, rather than suppression of protein processing, initiates the signal emanating from the ER culminating in eIF-2 alpha phosphorylation and translational repression.

Animals↗
PubMed1985

Dengue virus induced polypeptide synthesis. Brief report.

Dengue 2 virus polypeptide synthesis was investigated in BHK21 cells. Nine or ten virus induced polypeptides were identified, three of which are glycoproteins as demonstrated by tunicamycin treatment of infected cells. We performed pulse chase experiments, experiments with amino-acid analogs, protease inhibitors or pactamycin treatment of infected cells, to determine whether or not large polypeptide processing occurs. In some of these experiments a large polypeptide (P 130) was immunoprecipitated by an anti-dengue 2 serum. We observed a transfer of label between small molecular weight polypeptides which might be the result of restricted proteolytic cleavage.

Animals↗
PubMed1980

Combined antiviral effect of DNA inhibitors on Herpes simplex virus multiplication.

The inhibition of herpesvirus type 1 in cell cultures by seven inhibitors of DNA synthesis and by pactamycin was investigated by plaque inhibition in Vero cells with agarose overlay, and by yield reduction in one-step growth in HeLa cells. While the plaque inhibition method proved to be suitable to show inhibition by single substances, only the yield reduction procedure was reliable for investigating the interaction of two substances. Inhibition was evaluated by means of an inhibition quotient (number of PFU in uninhibited virus controls:number of PFU in test specimen); combined inhibition was related to results with single substances. Among the 28 substance pairs, 9 cases of indifference, 10 additive, and 9 synergistic interactions were found. Indifference was observed only with fluorodeoxyuridine and amethopterin as one of the partners, which by themselves inhibited herpesvirus multiplication incompletely.

Animals↗
PubMed1976

Some properties of the small homodisperse RNAs in the cytoplasm of HeLa cells.

Two homodisperse, methylated, small molecular weight RNAs, that have been previously described in HeLa cells and that are apparently coded by the nuclear genome, appear in the cytoplasm shortly after transcription and are detected in the cytoplasm with a half-life of a few minutes. Under the denaturing conditions of urea-polyacrylamide gel electrophoresis, the migration of these RNAs indicated nucleotide lengths around 190 (A) and 160 (B). Neither A nor B RNAs differed in their electrophoretic mobility when comparing samples from 10 to 120 min incubation with [3H]uridine. When the detergent-treated postmitochondrial fraction from cells incubated for 60 min with [3H]-uridine was centrifuged through a 0.3 M NaC1/0.5 M sucrose cushion, the resulting pellet showed a marked increase in the ratio of counts A/4 S RNA, and particularly B/4 S RNA, suggesting that these RNAs might not exist free in the cytoplasm. At low concentrations of camptothecin (1-2.5 mug/ml), the accumulation of A and B RNA was greatly suppressed, while the synthesis of 4 S and 5 S RNA was less affected. Their accumulation (particularly that of B RNA) was enhanced when cells were exposed to inhibitors of various steps of protein synthesis (puromycin, cycloheximide, pactamycin, emetine). Pulse-chase experiments with actinomycin D during suppression of protein synthesis indicated that, at least in the case of B RNA, this increased accumulation was due, at least partly, to a marked prolongation of its half-life.

Camptothecin↗
PubMed1977

An ATP-dependent inhibition of protein synthesis in ascites cell extracts by wheat germ protein.

A high speed supernatant fraction from wheat germ was shown to be a very effective inhibitor of protein synthesis in a cell-free protein synthesizing system from Ehrlich ascites cells. Low concentrations of the extract were equally effective in inhibiting the translation of EMC viral RNA, ascites cell mRNA (exogenous) and endogenous mRNA. The kinetics of inhibition in the presence and absence of pactamycin, as well as the observed inhibition of polyphenylalanine synthesis, indicate that the wheat germ inhibitor acts at the level of elongation. Preincubation of the ascites system with the wheat germ inhibitor in the presence and absence of ATP showed that ATP was required for the development of the inhibition. The inhibitor was partially purified and appears to be a basic protein with a molecular weight of 30 000--40 000. These results are discussed with respect to the hypothesis that this may be another example of a protein kinase-induced inhibition of protein synthesis.

Adenosine Triphosphate↗
PubMed1984

Superinduction of human interleukin-2 messenger RNA by inhibitors of translation.

Stimulation of human lymphocytes with phytohemagglutinin results in the induction of messenger RNA encoding interleukin-2 (IL-2), a lymphokine possessing immuno-regulatory properties. We have previously demonstrated a dramatic superinduction of the formation of IL-2 and of biologically active IL-2 mRNA in the presence of cycloheximide, an inhibitor of translation. These findings suggested the involvement of a labile protein repressor in the regulation of human IL-2 gene expression. Here, we show a commensurate superinduction of IL-2 mRNA sequences by three additional inhibitors of protein synthesis with distinct modes of action: T-2 toxin, pactamycin, and sparsomycin. These results strengthen the concept that a labile protein controls the formation of mature IL-2 mRNA. They tend to eliminate the possibility that the superinduction phenomenon observed in the presence of cycloheximide is due to its action on a process other than translation.

Cells, Cultured↗