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At least 523 records · Page 29Linked to original sources
PubMed1992

Differential regulation of fos and jun gene expression and AP-1 cis-element activity by endothelin isopeptides. Possible implications for mitogenic signaling by endothelin.

Endothelins (ET) are potent vasoconstrictor peptides that also function as mitogens for numerous cell types. Although regulation of second messenger pathways by ET peptides has been extensively investigated, little is known about the pathways of nuclear signaling by which ET controls gene expression. The present experiments investigated whether fos and jun contribute to nuclear signaling and gene regulation by ET isopeptides. ET isopeptides induced a subset of fos and jun mRNAs in mesangial cells, including c-fos, fra-1, c-jun, and JunB. fos and jun mRNAs were induced as members of the immediate-early gene response. Activation of the high affinity ET receptor moderately increased c-fos and fra-1 mRNA, whereas activation of the low affinity receptor markedly induced both fos and jun mRNAs. Thus, different ET receptor subtypes evoke distinct patterns of fos and jun induction. Prominent isopeptide- and cell-specific differences in the magnitude and kinetics of fos and jun expression were observed. Most striking was the marked elevation of c-fos steady-state mRNA and protein by ET-1, as compared with ET-3. In addition, ET-1, but not ET-3, increased transcriptional activity conferred by an AP-1 cis-element and directed collagenase gene expression. These results suggest that differential regulation of fos and jun expression and of AP-1 cis-element activity by ET isopeptides contributes to regulation of gene expression by ET. Furthermore, a role for AP-1 in mitogenic signaling by ET is suggested by the close correlation between AP-1 cis-element activity and cell growth.

3T3 Cells↗
PubMed1990

Mapping of functional domains in Fos and Jun proteins using epitope-specific antibodies.

A panel of epitope-specific antibodies, directed against c-Fos, c-Jun, and FosB derived oligopeptide sequences, was generated and used to study the interaction of Fos and Jun proteins and the binding of the Fos/Jun complex to the AP1-binding site (TRE). Our results strongly support results previously obtained by site-directed mutagenesis experiments. The leucine zipper is the major site of interaction between Fos and Jun. Antibodies directed against this domain of Fos bound free Fos protein efficiently, but were unable to recognize Fos within the Fos/Jun complex. In contrast, all other Fos epitope-specific antibodies showed similar reactivity with both free and complexed Fos. Antibodies directed against sequences adjacent to the leucine zipper inhibited formation of the complex. This may suggest that amino acids in the vicinity of the leucine zipper may also play some role in the formation of the protein complex. Binding of Fos/Jun to the TRE was inhibited only by antibodies directed against the basic regions in Fos or Jun previously suggested to represent the DNA binding sites. The fact that very similar results were obtained by two totally different strategies, i.e., mutagenesis experiments and domain mapping using epitope-specific antibodies, lends strong support to the proposed domain structure of Fos and Jun family members.

Amino Acid Sequence↗
PubMed1991

In vitro transcriptional analysis of the human c-fos proto-oncogene.

The transcription of the human c-fos promoter was characterized in vitro using HeLa nuclear and whole cell extracts. The c-fos gene and c-fos promoter fusions to the SV40 early region and the G-free cassette were active as templates, yielding faithfully initiated transcripts that were sensitive to alpha-amanitin. c-fos-SV40 and -G-free cassette templates were less efficiently transcribed when linearized, suggesting that template topology affected fos activity in vitro. Transcription conditions were optimized for both extracts using a mixture of the fos wild type promoter, a deleted fos promoter retaining just the TATA box, and the adenovirus major late promoter, all driving differently sized G-free cassettes. The fos promoter was inactive at low protein and DNA concentrations, and then showed a sharp rise in efficiency with a subsequent 2-fold increase in the amount of either DNA or protein. In contrast, high protein or DNA concentrations were required for the deleted fos promoter to show only weak activity. Preincubation of templates with extracts shortened the lag time before transcription could be detected, but did not lead to increased activity. By comparing reactions in the presence and absence of Sarkosyl, we estimate that only a subset of fos-driven templates was active, and that these templates were used for several rounds of transcription.

Amanitins↗
PubMed1991

c-fos transcriptional activation by IL-2 in mouse CTL-L2 cells is mediated through two distinct signal transduction pathways converging on the same enhancer element.

The c-fos protooncogene is suspected to play a major role during the activation of cells from different lineages. In particular, c-fos transcription is induced upon entry into a proliferation cycle in a wide variety of cell types. In this study, we have transfected an IL-2-dependent murine T cell line with chloramphenicol acetyl transferase (CAT) reporter constructs, harboring various regions of the human c-fos promoter. We show that IL-2 induces activation of fos CAT reporter constructs in these cells. Furthermore, the induction by IL-2 is mediated through a dyad symmetry element, the serum response element, which is also responsible for fos CAT reporter constructs activation by PMA, a pharmacologic activator of the protein kinase C (PKC). To assess any involvement of PKC in signal transduction for fos CAT reporter activation by IL-2, CTL-L2 cells were PKC-depleted by treatment with high doses of PMA. Such a treatment abolished the transcriptional response of fos CAT reporter constructs to PMA. In contrast, IL-2 was still able to activate fos CAT transcription, albeit with a lower efficiency. These results suggest that PMA-sensitive PKC might be part of intracellular transduction pathways leading to c-fos transcriptional activation by IL-2, and that at least one alternate pathway participates in the complete response. However, these distinct signal transduction pathways have the same DNA target on c-fos promoter, the serum response element.

Animals↗
PubMed1990

Chemical carcinogenesis is accelerated in c-fos transgenic mice.

Transgenic mice, having mouse proto-oncogene c-fos under the control of the promoter from murine major histocompatibility complex (MHC) class I gene (H2-Kb), have been established (c-fos mouse). C-fos mouse have been shown to produce high amount of exogenous c-fos protein in various organs. However, they do not develop any malignant tumors. In order to examine the effect of c-fos protein in oncogenesis, dorsal skin or lower gingiva of the mice were scratched and painted with 9,10-dimethyl-1,2-benzanthracene (DMBA) twice a week. C-fos mice showed squamous cell carcinoma in both skin and gingiva at 8 weeks after the treatment. On the contrary, control litter mate did not show any malignant change even at 11 weeks after the treatment. These results indicate that chemical carcinogenesis is accelerated in c-fos mice. Since the activities of immunosurveillance (e.g. natural killer (NK) cell and cytotoxic T lymphocyte (CTL)) in spleen cells from c-fos mice were significantly lower than those from control litter mate, effects of both the abnormal amount of c-fos protein and the partial defect of immunosurveillance in c-fos mice accelerate the induction of neoplasms in epithelial cells stimulated with DMBA.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1994

Protein c-fos induction in rat brain and spinal dorsal horn by sincalide and opioids in vitro.

Sincalide (CCK-8) is an antiopioid substance. In this study, we investigated the effects of sincalide and opioids on c-fos expression and their interaction in brain and spinal dorsal horn in vitro. Immunoprecipitation was used for detection of c-fos protein. The results indicated that 0.1 mumol.L-1 sincalide induced c-fos expression markedly in both brain (a 3.8-fold increase in c-fos protein level) and in spinal dorsal horn (a 3.6-fold increase). NDAP (a kappa receptor agonist) 0.1 mumol.L-1 showed some activating effects on c-fos expression, the c-fos protein level increased 2.7 and 2.6 times respectively in brain and spinal dorsal horn. Ohmefentanyl (Ohm, a mu receptor agonist) 0.1 mumol.L-1 also exhibited an inducing effect on c-fos protein production. Sincalide and NDAP exerted some additive effects on c-fos protein production in spinal cord. In contrast, the effect of sincalide on c-fos protein production is antagonistic to that of Ohm. The results suggested that there were changing patterns of interaction on c-fos expression between sincalide and opioids.

Animals↗
PubMed1995

Progesterone enhances an estradiol-induced increase in Fos immunoreactivity in localized regions of female rat forebrain.

In female rats, the onset of reproductive behavior depends on the sequential presence of estradiol followed by progesterone. Although treatment with high doses of estradiol has been shown to increase immunostaining for the Fos protein, an immediate early gene product that is expressed upon cellular activation, another report conflicts with this finding. However, the previous reports agree that subsequent treatment with progesterone has no apparent effect on Fos expression. In order to resolve this discrepancy and investigate possible effects of progesterone, we used Fos immunocytochemistry combined with computer-aided image analysis. In experiment one, we found that treatment with 5 micrograms of estradiol increased Fos immunoreactivity (Fos-IR) within a section of the medial preoptic area and the dorsal medial hypothalamus. Subsequent treatment with 500 micrograms of progesterone 1 hr before perfusion increased the intensity of the immunostaining within the medial preoptic area and the dorsal medial hypothalamus, although it had no significant effect on Fos-IR cell number. In experiment 2, a lower concentration of Fos antiserum was used in order to diminish the immunostaining sensitivity to a level in which no increase of Fos-IR cell number was observed after treatment with estradiol. Under these immunocytochemical conditions, subsequent treatment with progesterone increased the number of Fos-IR cells in the medial preoptic area, the dorsal medial hypothalamus and the steroid receptor-rich area lateral to the ventromedial hypothalamus. Thus, treatment with behaviorally effective doses of both estradiol and progesterone induces Fos expression in localized regions of female rat brain.

Animals↗
PubMed1994

Distribution of fos-like immunoreactivity in the medullary and upper cervical dorsal horn produced by stimulation of dural blood vessels in the rat.

Neurophysiological studies have generally failed to find evidence of a specific ascending pathway for visceral nociception. However, pain that arises from deep or visceral tissues typically differs from cutaneous pain, particularly in its diffuse, poorly localized quality. In this study, the c-fos mapping technique was used in order to investigate possible differences in the distribution of central neurons activated by afferent pathways from cutaneous and deep tissues that may be related to the differing quality of the sensations they evoke. The distribution of neurons in the upper cervical and medullary dorsal horn that displayed fos-like immunoreactivity (fos-LI) was examined following mechanical stimulation of dural blood vessels (transverse and superior sagittal sinuses), and was compared to that found following mechanical, thermal, and chemical stimulation of facial sites. Dural stimulation was carried out Brevital anesthesia in rats that had received a chronic surgical exposure of the transverse and superior sagittal sinuses 2 d earlier. Localized mechanical stimulation of the dural surface of the transverse sinus produced a predominantly ipsilateral increase in the number of fos-LI neurons in the medullary and upper cervical dorsal horn (primarily laminae I and V), and in the transition region between the trigeminal nucleus caudalis and interpolaris. Stimulation of the superior sagittal sinus produced increases in fos-LI labeling that were generally smaller than those produced by transverse sinus stimulation. The distribution of fos-LI labeling in the dorsal horn induced by dural stimulation differed from that induced by facial stimulation in two ways. (1) Dural stimulation produced a more diffuse distribution of fos-LI than facial stimulation in the dorsal horn. Whereas facial stimulation produced a dense, localized zone of fos-LI labeling in the dorsal horn, dural stimulation produced fos-LI labeling that extended from the midlevel of caudalis to C2/C3, and also extended across a large portion of the ventrolateral-to-dorsomedial axis of the dorsal horn. This distribution roughly corresponds to the representation of most of the dorsal half of the head and face. (2) Dural stimulation produced a more restricted laminar distribution of fos-LI labeling than facial stimulation, in that the dural-induced labeling in the superficial dorsal horn was primarily restricted to lamina I, whereas facial stimulation typically induced substantial labeling in both lamina I and the outer part of lamina II. These differences in the central organization of the afferent pathways from dural and facial sites may contribute to the differences in the quality of sensations evoked by these pathways.

Animals↗
PubMed1993

Distribution pattern of c-Fos expression induced by sciatic nerve sectioning in the rat central nervous system.

c-Fos expression in the rat central nervous system following sciatic nerve section was compared using an immunohistochemical procedure with control skin-incisions. c-Fos-immunoreactive (IR) materials were localized in the nuclei of nerve cells, and these positive cells were most abundantly observed 120 min after the operation. In the spinal cord, c-Fos-IR cells were seen in the posterior horn on the operated, but not in the contralateral side. The anterior horn and the dorsal root ganglia did not contain c-Fos-IR cells. The experimental animals had the largest number of c-Fos-IR cells in the lumbosacral segments, especially in laminae I and II of L4 and L5 segments. The difference in the number of c-Fos-IR cells and IR intensity between the experimental and control animals was conspicuous in the lumbosacral segments, but there was no significant difference between them in the cervical and thoracic segments. In the brain, an apparent difference in positive cell distribution was not recognized between the experimental and control animals. c-Fos-IR cells were observed in various regions of the brain. A high concentration of positive cells was seen in the temporal cortex, the clastrum, the lateral septal nucleus (ventral part), the hypothalamic nuclei such as periventricular, suprachiasmatic, paraventricular, arcuate, dorsomedial and supramammillary nuclei, the paraventricular thalamic nucleus, the ventral lateral geniculate nucleus (magnocellular part), the pontine nuclei, the dorsal and dorsolateral tegmental nuclei, the parabrachial nucleus (Kölliker-Fuse nucleus), the locus coeruleus, and the nucleus of the solitary tract. Among them, the paraventricular and suprachiasmatic hypothalamic nuclei exhibited the most dense concentration of c-Fos-IR cells and intensity. These results indicate that the c-Fos expression in the brain is induced by transsynaptic stimulation. The findings that there was a clear difference in the distribution of c-Fos-IR cells and in intensity between the experimental and control animals in the lumbosacral segment of the spinal cord but not in the upper portion and the brain, suggested that there is poor discrimination of nociceptive information in the brain between stimulation by nerve section and skin-incision.

Animals↗
PubMed1993

Topographic patterns of brain activity in response to swim stress: assessment by 2-deoxyglucose uptake and expression of Fos-like immunoreactivity.

Alterations in brain activity patterns were assessed in response to swim stress by immunocytochemical detection of Fos-like immunoreactivity (Fos-LI) and high-resolution autoradiographic imaging of 14C-2-deoxyglucose (2-DG) uptake. The stress paradigm investigated was a classic behavioral screen for antidepressant drug activity, the forced swim test. One of the most pronounced effects produced by swim stress was an increase in 2-DG uptake and induction of Fos-LI in a restricted region of the lateral septal nucleus. Specific "limbic" cortical regions, including the medial prefrontal, ventrolateral orbital, and cingulate cortices, also exhibited both increased 2-DG uptake and expression of Fos-LI in response to swim stress. In the hypothalamic paraventricular nucleus of swim-stressed rats, Fos-LI was induced but no change in 2-DG uptake was apparent. Since the specific swim stress protocol used is a behavioral screen for antidepressant drugs, the effects of imipramine on stress-induced alterations in 2-DG uptake and induction of Fos-LI were examined. The stress-induced increase in 2-DG uptake in the lateral septum was blocked by treatment with imipramine, but treatment with imipramine had no effect on induction of Fos-LI in the same region. Neither 2-DG uptake nor Fos-LI expression was altered by imipramine treatment in the cortical regions influenced by swim stress. Administration of imipramine alone under basal conditions produced a robust induction of Fos-LI in the central nucleus of the amygdala and in the dorsal lateral subdivision of the bed nucleus of the stria terminalis. No effect of imipramine treatment on 2-DG uptake was apparent in these latter regions. The results provide insights into topographic patterns of brain activity associated with swim stress and neuroanatomically selective actions of imipramine. The different and complementary information obtained by assessment of Fos-LI and 2-DG uptake illustrates the utility of applying both functional mapping approaches to examine neuroanatomical correlates of behavioral states and drug treatment.

Amygdala↗
PubMed1996

Persistent c-fos expression in the brains of mice with chronic social stress.

The present study was conducted to demonstrate immunohistochemically, the sites of c-fos protein expression in the brains of mice subjected to acute and chronic social defeat stress. To induce social stress, mice were placed in situations of species-specific intermale aggression either only once or five times at 24 h intervals. Two hours after the single or fifth defeat stress, many c-fos immunoreactive neurons were observed in a variety of brain regions including the limbic system and sensory relay nuclei. The c-fos immunoreactive neurons in the brains of acute defeat mice decreased in number with time and the c-fos staining pattern of acute defeat mice became indistinguishable from that of normal control mice by 24 h after the single defeat stress. In contrast, chronic defeat stress induced persistent c-fos expression in the forebrain and brainstem even 24 h after the fifth defeat stress. In the forebrain of chronic defeat mice, the olfactory bulb, cingulate cortex, hippocampus, entire hypothalamus, septal nuclei and the amygdaloid complex, except for the central nucleus, were labeled intensely with c-fos antiserum. In the lower brainstem, nerve cells with c-fos immunoreactivity were seen mainly in ascending and descending sensory relay nuclei relevant to auditory and vestibular transmission, epicritic sensation (gracile and external cuneate nuclei), pain inhibition (central gray and raphe nuclei), and viscerosensory transmission (solitary tract nucleus). The differences in c-fos expression among the normal control, acute and chronic defeat mice were evaluated by an enumeration of the immunopositive neurons within each brain nucleus examined, and they were confirmed subsequently by statistical analysis. There was little c-fos expression in the nucleus putamen, lateral, ventral and posterior thalamic nuclei, pretectal nuclei, medial geniculate nucleus, red nucleus, substantia nigra, cerebellum, spinal cord, or cranial nerve nuclei. These findings suggest that chronic but not acute defeat stress causes persistent c-fos expression in more widespread brain regions than do any other stresses so far investigated. The present study may shed light on the central mechanisms by which behavioral abnormalities and/or chronic sociopsychological stress leads to the occurrence of abnormal behavior and/or psychosomatic disorders in experimental animals and humans.

Animals↗
PubMed1997

Dopamine-adenosine interactions in the striatum and the globus pallidus: inhibition of striatopallidal neurons through either D2 or A2A receptors enhances D1 receptor-mediated effects on c-fos expression.

D1 receptors located on striatonigral neurons and D2 receptors located, together with A2A receptors, on striatopallidal neurons are known to interact functionally. Using in situ hybridization, we examined the effects of D1 and D2 agonists and of an A2A antagonist on c-fos mRNA in identified striatal neurons and in globus pallidus. The full D1 agonist, SKF 82958 (1 mg/kg), induced a homogenous increase of c-fos mRNA in the striatum. This increase occurred to a similar extent in D1 and D2 receptor-containing striatal neurons. Conversely, the D2 agonist, quinelorane (2 mg/kg), decreased c-fos mRNA in these populations but increased it in globus pallidus. The adenosine A2A receptor antagonist, SCH 58261 (5 mg/kg), also decreased c-fos mRNA in D2 receptor-containing neurons in striatum but did not affect pallidal c-fos mRNA. Concomitant administration of either D1 plus D2 agonists or D1 agonist plus A2A antagonist caused a potentiation of c-fos mRNA in striatal neurons expressing the D1 receptor and in globus pallidus. However, only the combination of D1 and D2 agonists modified the c-fos mRNA expression to a "patchy" distribution. Our data show that (1) c-fos expression can be activated through D1 and inhibited through A2A or D2 receptors in both striatal output pathways in normal rats, and (2) D2 receptor stimulation as well as A2A receptor blockade can interact with D1 receptor activation to potentiate c-fos expression in the striatum and the globus pallidus. The data also suggest that the topological alteration of c-fos expression after coadministration of D1 and D2 agonists involves D2 receptors located on interneurons or presynaptically on dopaminergic nerve terminals.

Adenosine↗
PubMed1998

Induction of Fos-like proteins and ultrasonic vocalizations during ethanol withdrawal: further evidence for withdrawal-induced anxiety.

The ethanol withdrawal syndrome includes anxiety as a prominent symptom. Because the extent that specific regions of brain are critical to the generation of this emotional state is unknown, Fos-like immunoreactivity (Fos-LI) was used to associate specific regions of the rat brain with the anxiety component of the ethanol withdrawal syndrome exacerbated by an air puff challenge in rats. Chronic ethanol liquid diet was administered intragastrically for 4 days or by having the rats consume the diet for 14 days. During withdrawal from either treatment protocol, Fos-LI was induced most prominently in forebrain areas, although the midbrain and hindbrain were also represented. Included in these Fos-LI positive regions were many cortical regions, septum, accumbens, claustrum, amygdala, paraventricular nucleus of the thalamus and hypothalamus, hippocampus, locus coeruleus, and central gray. Fos-LI expression differed mostly in intensity between the two treatment and withdrawal protocols, with the gastric protocol producing the greatest Fos-LI induction in most brain regions. The threshold for air puff-induced ultrasonic vocalizations was decreased, and the number of vocalizations was increased and the period of vocalization was extended. These behavioral data indicate that aversively motivated responding in rats during ethanol withdrawal can be readily quantified with the ultrasonic vocalizations test without precipitating convulsive activity. Furthermore, a comparison of the effects of the air puff challenge versus withdrawal on Fos-LI indicated that the behavioral state induced in these two situations share functional neuroanatomical features. Some regions--such as the accumbens core, medial septum, subregions of the amygdala, hippocampus, substantia nigra, and cerebellum--exhibited little Fos-LI during withdrawal and also did not exhibit strong increases after the addition of the air puff challenge. However, other regions-such as the cerebral cortex (medial prefrontal, frontal, cingulate and ventrolateral orbital, claustrum, and tenia tecta), hypothalamus, and locus ceoruleus- exhibited Fos-LI at levels higher than that seen after either the ethanol withdrawal or puff challenge alone. These overlapping patterns of Fos-LI in specific regions of the brain, activated by both ethanol withdrawal and an anxiety provoking behavioral challenge, suggest that specific neuroanatomical sites in brain are associated with the symptom of anxiety observed during the "ethanol withdrawal syndrome."

Alcohol Withdrawal Delirium↗
PubMed1985

Product of the cellular oncogene, c-fos, observed in mouse and human tissues using an antibody to a synthetic peptide.

The transforming gene of the osteosarcoma-producing FBJ murine sarcoma virus, v-fos, is homologous to a normal cellular gene, c-fos, in vertebrate species. Transcripts from the c-fos proto-oncogene accumulate to very high levels in late gestational mouse and human extra-embryonic tissues. We now report that these RNA transcripts are translated in these tissues. Rabbits were immunized with a synthetic peptide whose sequence is common to both c-fos and v-fos. After affinity purification on an immunosorbent containing the fos peptide (a nonapeptide), the antibody reacted with a component(s) in nuclei in sections of human and murine tissues and immunoprecipitated the v-fos gene product (p55) and a cellular protein of 39 kd (p39, complexed with fos) from lysates of metabolically-labelled virally transformed cells. Crude extracts of normal tissues contained major anti-fos-reactive proteins in the range of 55-60 kd as shown by protein blot analysis. Indirect immunofluorescence and immunoperoxidase staining showed that in addition to strong immunoreactive component(s) in the nuclei of extra-embryonic tissues of human and mouse, weaker reactions are detectable in all normal fetal and adult tissues tested. This demonstrates that fos-reactive protein is expressed in a wide variety of cells and tissues.

Amino Acid Sequence↗
PubMed1987

Transcriptional induction of proto-oncogene fos by HSV-2.

HSV-2 induces the transcription of c-fos gene in both human (diploid) cell strains and mouse (heteroploid) cell lines. HSV-1 is incapable of such induction. The induction of transcription is rapid and transient in both cell types. The product of transcriptional induction of c-fos in mouse cells is mainly a 4.5 kb fos mRNA along with lesser amount of a 2.2 kb fos mRNA, while in human cells the 4.5 kb mRNA is the only detectable product. Both the 4.5 kb and 2.2 kb fos mRNAs are mature gene products as judged by their presence exclusively in the cytoplasm of infected mouse L929 cells, while a 3.5 kb putative precursor of the 2.2 kb fos mRNA appears exclusively in the nucleus. In infected human WI38 cells, the 4.5 kb mRNA also appears exclusively in the cytoplasm. Virus specific protein synthesis is an absolute requirement for the transcriptional activation. The 4.5 kb fos mRNA is under different control mechanisms since it is not induced by serum stimulation of serum starved cells as is the 2.2 kb fos transcript. Moreover, in serum starved cells simultaneously stimulated by serum and infected, only the 2.2 kb fos transcript can be superinduced by the protein synthesis inhibitor cycloheximide, while the appearance of the 4.5 kb fos mRNA is completely blocked by this treatment.

Animals↗
PubMed1985

Rapid induction of the expression of proto-oncogene fos during human monocytic differentiation.

The differentiation into macrophages of the monocytic cell line U-937 or the monomyelocytic cell line HL-60 induced by phorbol esters is accompanied by a rapid induction of the expression of the proto-oncogene c-fos. Maximal levels of c-fos gene transcripts accumulate within 20-30 min following induction. By 2 hr, the c-fos-specific mRNA level drops 5 to 10 fold below that detected at 30 min after induction. The concentration of c-fos mRNA remains unchanged for the next 5 days, at which time over 99% of the viable precursor cells are converted to adherent macrophages. c-fos protein can be detected within 20 min of induction, reaching maximal levels by 40-60 min. Little or no c-fos protein is detected by 120-150 min after induction, even though c-fos mRNA remains detectable. Presence of cycloheximide leads to superinduction of c-fos mRNA transcripts. No c-fos gene transcripts are detected when the HL-60 cell line is induced with Me2SO to differentiate to granulocytes. A role for the c-fos protein is envisaged in the monocyte differentiation pathway.

Cell Differentiation↗
PubMed2001

Allodynia and hyperalgesia produced by specific inhibition of spinal c-fos expression: lack of correlation with dynorphin content.

Inhibition of spinal Fos expression increases formalin-induced nociception and decreases spinal prodynorphin messenger ribonucleic acid (mRNA), suggesting that Fos modulates nociception by inducing dynorphin synthesis. This study tests the hypothesis that Fos modulates sensitivity to other somatic stimuli, such that inhibition of Fos expression will result in tactile allodynia and thermal hyperalgesia. In addition, it correlates the somatosensory effects of inhibition of Fos expression with spinal dynorphin content. Antisense oligodeoxynucleotide (ODN) to c-fos mRNA was administered by intrathecal infusion. Tactile sensitivity was tested by probing the hindpaw with von Frey filaments. Thermal sensitivity was quantitated by using withdrawal latency to radiant heat. Two percent formalin was injected into the dorsal hindpaw, and flinches were quantitated. Fos was quantitated by counting immunoreactive cells. Dynorphin was measured by immunoassay. Intrathecal antisense, but not mismatch, ODN resulted in tactile allodynia, thermal hyperalgesia, and hyperalgesia to formalin-induced nociception. Antisense ODN decreased Fos-like immunoreactivity after formalin injection but did not alter Jun-like immunoreactivity. Antisense ODN had differing effects on spinal dynorphin content, depending on the method of administration. These experiments show a role of Fos in modulating somatosensory sensitivity and suggest that induction of dynorphin synthesis is not the sole mechanism by which Fos does so.

Journal Article↗
PubMed1986

Transcriptional activation encoded by the v-fos gene.

We present evidence that the fos oncogene encodes a transcriptional trans-activation function. trans-activation was assayed by cotransfection into NIH 3T3 mouse fibroblasts of v-fos DNA containing plasmids together with a plasmid containing a test promoter. Three v-fos DNAs were used: (i) pFBR-1, a plasmid containing the FBR proviral sequences; (ii) pFBJ-2, a plasmid harboring the FBJ proviral sequences; (iii) pMF-J, a plasmid containing the FBJ fos sequences linked to a mouse metallothionein promoter. Each of the three v-fos DNA plasmids stimulated the expression of a cotransfected chimeric gene consisting of a promoter segment of the mouse alpha 1(III) collagen gene linked to the gene for chloramphenicol transacetylase. In similar experiments the v-fos gene also stimulated the long terminal repeat promoter of Rous sarcoma virus (RSV) but neither the early promoter of simian virus 40 nor the beta-actin promoter. Evidence that the trans-activation function is specified by the v-fos coding sequences comes from the fact that a frameshift mutation in the v-fos coding sequence inhibits the trans-activation. Two mutations that map around nucleotide -100 in the RSV promoter do not respond to cotransfection with v-fos, whereas other mutations respond like the wild-type RSV promoter. These experiments suggest that the v-fos gene either encodes or induces an activator of transcription that recognizes specific sequences in promoters.

Animals↗