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PubMed2006

Acute suppression, but not chronic genetic deficiency, of c-fos gene expression impairs long-term memory in aversive taste learning.

Several lines of evidence have indicated that the establishment of long-term memory requires protein synthesis, including the synthesis of immediate-early gene products. Although the anatomical expression patterns of the c-fos gene, a transcription factor-encoding immediate-early gene, in conditioned taste aversion (CTA) are well documented, the functional roles of c-fos gene expression and Fos-mediated transcription remain to be clarified. Using the antisense oligodeoxynucleotide (AS-ODN) method in rats and gene-targeting knockout techniques in mice (c-fos(-/-) mice), we examined the roles of c-fos gene expression in the acquisition, retrieval, and retention of CTA. Preconditioning microinfusion of AS-ODN directed against c-fos mRNA (c-fos AS-ODN) into the parabrachial nucleus (PBN) impaired the acquisition, whereas infusion of control ODNs consisting of a randomized or inverted base order had no effect. Microinfusion of c-fos AS-ODN into either the amygdala or insular cortex did not impair the acquisition, whereas it attenuated the retention. Retrieval and subsequent retention of an acquired CTA were not disrupted by c-fos AS-ODN infusion into the PBN or amygdala. Microinfusion of another AS-ODN directed against zif268 (egr-1, krox-24, NGFI-A) mRNA into the PBN or amygdala did not affect the acquisition and retention. The genetic deficiency in c-fos(-/-) mice caused normal acquisition and retention. The present results suggest that the Fos-mediated gene transcription in the PBN, amygdala, or insular cortex plays critical roles in the acquisition and/or consolidation, but not the retrieval, of long-term taste memory; nevertheless, some other factors could compensate CTA mechanism when Fos-mediated transcription is not available.

Animals↗

PubMed1997

Activation of the human histamine H2 receptor is linked to cell proliferation and c-fos gene transcription.

We examined whether histamine could regulate cell proliferation and expression of the early response gene c-fos in HEK-293 cells stably transfected with the human H2 receptor (HEK-H2). Histamine stimulated [3H]thymidine incorporation [50% effective concentration (EC50) = 3.6 x 10(-6) M] in HEK-H2 cells in a cimetidine-sensitive manner and increased c-fos mRNA in a time-dependent fashion, reaching maximal induction after 30 min. Histamine induced luciferase activity in HEK-H2 cells transiently transfected with a construct containing the luciferase reporter gene (Luc) coupled to the serum response element (SRE) of the c-fos gene promoter (EC50 = 1.5 x 10(-6) M) or a plasmid containing the SRE core fragment (bases -320 to -298). The protein kinase C (PKC) inhibitor staurosporine and long-term pretreatment of HEK cells with phorbol ester inhibited the effect of histamine on PKC activation, SRE-Luc activity, and [3H]thymidine incorporation. We have demonstrated that activation of the human H2 receptor can lead to induction of c-fos gene transcription and cell proliferation through a PKC-dependent mechanism.

Cell Division↗

PubMed2006

Endothelin-1 and angiotensin II contribute to BNP but not c-fos gene expression response to elevated load in isolated mice hearts.

The early events in the cardiac hypertrophic process induced by hemodynamic load include activation of B-type natriuretic peptide (BNP) and c-fos gene expression. However, it is unknown whether stretch acts directly or through local paracrine factors to trigger changes in cardiac gene expression. Herein we studied the involvement of endothelin-1 (ET-1) and angiotensin II (Ang II) in load-induced activation of left ventricular BNP and c-fos gene expression using an in vitro stretch model in isolated perfused adult mice hearts. Two-hour stretch induced by increasing coronary flow rate from 2 to 5 ml/min increased the expression of BNP and c-fos genes by 1.9- and 1.5-fold, respectively (P<0.001 and P<0.05). A mixed ET(A/B) receptor antagonist bosentan attenuated the BNP gene expression response to load by 58% (P<0.005). A similar 53% inhibition was observed with the selective ET(A) receptor blocker BQ-123 (P<0.05). Type 1 Ang II receptor antagonist CV-11974 decreased the activation of BNP gene expression by 50% (P<0.05). In contrast, the activation of c-fos gene expression was not inhibited by antagonists of ET(A/B) and AT(1) receptors. Our results show that ET-1 and Ang II play a key role in the induction of BNP, but not c-fos gene expression in response to load in intact adult murine hearts.

Angiotensin II↗

PubMed2000

c-Fos gene expression pattern in the hypothalamus and the preoptic area of defeminized rats.

The object of the present study was to determine the c-fos gene expression pattern in the hypothalamus (HYP) and the preoptic area (POA) after estradiol and testosterone priming during the critical period of sexual differentiation of the rat brain. Three-day-old female rats were injected s.c. with a single dose of 17beta-estradiol (200 microg), testosterone enantate (200 microg) or vehicle (corn oil). HYP and POA were dissected 2 h, 24 h and 14 days after treatments and on the day of vaginal opening (VO). Other animals, previously treated as above, were acutely injected with 17beta-estradiol (5 microg) on the day of VO; HYP and POA were obtained 3 h later. Total RNA was extracted and processed for semiquantitative RT-PCR. We observed that c-fos gene expression was markedly increased in POA of the animals treated with estradiol or testosterone 2 h after treatments, while a non-significant increase in c-fos gene expression was observed in the HYP of these animals. We found a significant increase in c-fos expression in HYP and POA on the day of VO in both estradiol and testosterone defeminized rats. Interestingly, the acute estradiol administration on the day of VO did not induce c-fos gene expression in either HYP or POA of defeminized animals, instead a diminution in its expression was observed in animals treated with testosterone in POA. The overall results suggest that estradiol and testosterone imprinting during critical postnatal period of sexual differentiation of the brain permanently modifies the regulation of c-fos gene expression.

Animals↗

PubMed1993

Barrel rotation evoked by intracerebroventricular injection of somatostatin and arginine-vasopressin is accompanied by the induction of c-fos gene expression in the granular cells of rat cerebellum.

Intracerebroventricular (i.c.v.) injection of somatostatin (SS) or arginine-vasopressin (AVP) elicits barrel rotation (BR) in rats. To identify the potential neuron structures involved in this characteristic behavior, the regional expression of the c-fos gene in rat brain after i.c.v. injection of SS (10 micrograms) or AVP (1 micrograms) was examined by hybridization histochemistry. The c-fos expression could serve as a marker of neuronal activity and/or neural transmission. Following SS-induced BR, c-fos gene expression was observed in the lingula, uvula, nodulus, simplex, centralis, and culmen of the cerebellum, while following AVP-induced BR, c-fos gene expression was observed in the first four of the above-mentioned regions of the cerebellum, but not in the centralis or culmen. In these regions, the c-fos mRNA signals were observed on the granular layer. Expression of the c-fos gene was immediately and transiently induced and was not observed in rats in which BR was not evoked after SS or AVP injection. In both control rats and SS- or AVP-injected rats, the c-fos gene expression was induced in the piriform cortex and the flocculus of the cerebellum. The findings suggest that BR is a manifestation of behavior induced by massive transsynaptic activation of the granular cells in the cerebellum.

Animals↗

PubMed1990

Identification of an estrogen response element upstream of the human c-fos gene that binds the estrogen receptor and the AP-1 transcription factor.

Transcription of the proto-oncogene c-fos is stimulated by 17 beta-estradiol in estrogen responsive human and rat cells. To understand the molecular mechanisms of estrogen regulation of c-fos gene transcription, the human c-fos gene promoter, with 2.25 Kb of 5'-flanking DNA, was cloned upstream of the bacterial CAT gene and tested for estrogen regulation by transient transfection in HeLa cells. When an expression vector coding for the human estrogen receptor was co-transfected with the fos -CAT reporter, the promoter was found to respond to 17 beta-estradiol. An element responsible for estrogen induction was mapped in a 240 bp region localized 1060 to 1300 bases upstream of the startsite of transcription of the gene. Sequence analysis revealed, clustered in a 19 bp sub-region, a sequence corresponding to an imperfectly palindromic ERE: CGGCAGCGTGACC and two sequences: CTGAG and GTGAC, homologous to the core sequence of AP-1 transcription factor binding sites. A synthetic oligonucleotide reproducing this sub-region binds 'in vitro' both the estrogen receptor and AP-1 factor(s) and confers estrogen-responsivity to the HSV-tk gene promoter. Transcriptional activation by the estrogen receptor is prevented by mutations in the fos ERE that hamper binding of the receptor in vitro. Activation of the c-fos gene promoter in HeLa cells requires the DNA binding domain of the estrogen receptor, and can be achieved independently by the TAF-1 and the TAF-2 transcriptional activation functions of this molecule. A receptor mutant lacking the hormone binding domain can activate the c-fos gene promoter in the absence of estrogen.

Base Sequence↗

PubMed1990

Demonstration in living cells of an intragenic negative regulatory element within the rodent c-fos gene.

We studied c-fos gene expression in rat fibroblasts by microinjection of regulatory DNA sequences, such as the serum response element (SRE) present in c-fos promotor, in order to compete directly with such sequences for binding of putative regulatory factors. We show that an additional fos intragenic regulatory element (FIRE) is located at the end of exon 1. When coinjected with an SRE oligonucleotide, it induced c-fos expression in quiescent cells, whereas injection of SRE sequence alone failed to do so. Moreover, injection in quiescent cells of an SRE oligonucleotide together with a p-fos-lacZ construct containing the c-fos SRE as well as an in-frame insertion of FIRE resulted in a block to beta-galactosidase expression that can be relieved by coinjection of the FIRE sequence.

Animals↗

PubMed1991

Inhibition of jun transformation by a mutated fos gene: design of an anti-oncogene.

The protein products of the fos and jun oncogenes (Fos and Jun) function as transcriptional regulators in the form of homo- or heterodimeric complexes that bind to DNA. Dimerization is mediated by a leucine zipper structure that serves to juxtapose alpha-helical regions of each protein, rich in basic amino acids, that form a bipartite DNA-binding domain. Although Fos participates exclusively in heterodimeric complexes, Jun can function either as a homodimer that has a low apparent affinity for DNA or as a more stable heterodimer with Fos that has a higher apparent affinity for DNA. We have used these properties of Fos and Jun to design a mutated fos gene, lacking a functional DNA-binding domain (supfos1), that suppresses the transforming activity of jun in trans. Here we show that chicken embryo fibroblasts transformed by jun revert to a normal phenotype after infection by a retroviral vector encoding supFos1. Furthermore, infection of normal cells with the supfos1 vector renders them resistant to subsequent transformation by jun. Inhibition of jun transformation was associated with the appearance of supFos1-Jun heterodimers and a reduction in the AP-1 DNA-binding activity contributed by Jun homodimers. These findings demonstrate that the function of leucine zipper-containing transcription factors can be investigated by the procedure of intracellular immunization.

Animals↗

PubMed1999

L-Type Ca(2+) channels are essential for glutamate-mediated CREB phosphorylation and c-fos gene expression in striatal neurons.

The second messenger pathways linking receptor activation at the membrane to changes in the nucleus are just beginning to be unraveled in neurons. The work presented here attempts to identify in striatal neurons the pathways that mediate cAMP response element-binding protein (CREB) phosphorylation and gene expression in response to NMDA receptor activation. We investigated the phosphorylation of the transcription factor CREB, the expression of the immediate early gene c-fos, and the induction of a transfected reporter gene under the transcriptional control of CREB after stimulation of ionotropic glutamate receptors. We found that neither AMPA/kainate receptors nor NMDA receptors were able to stimulate independently a second messenger pathway that led to CREB phosphorylation or c-fos gene expression. Instead, we saw a consecutive pathway from AMPA/kainate receptors to NMDA receptors and from NMDA receptors to L-type Ca(2+) channels. AMPA/kainate receptors were involved in relieving the Mg(2+) block of NMDA receptors, and NMDA receptors triggered the opening of L-type Ca(2+) channels. The second messenger pathway that activates CREB phosphorylation and c-fos gene expression is likely activated by Ca(2+) entry through L-type Ca(2+) channels. We conclude that in primary striatal neurons glutamate-mediated signal transduction is dependent on functional L-type Ca(2+) channels.

Animals↗

PubMed2001

Expression of the c-myc and c-fos genes as a potential indicator of late radiation damage to the kidney.

PURPOSE: To evaluate proliferative response according to c-myc and c-fos gene expression as an early indicator of late radiation damage to the kidney. METHODS AND MATERIALS: c-myc and c-fos gene expression was measured in the irradiated kidney of C3H/HeSlc mice using reverse transcriptase-polymerase chain reaction (RT-PCR) 24 h after 9, 12, and 15 Gy as well as 2 and 7 days after 15 Gy. In a second experiment, 12 Gy was administered to the right kidney plus the lower half of left kidney. The mice underwent left nephrectomy 24 h after, and the correlation between increased gene expression and elevation of the blood urea nitrogen (BUN) level representing late functional damage was investigated. RESULTS: c-myc and c-fos expression increased in 1 of 10 controls and in 8 of 10 and 7 of 10 mice that received 15 Gy, respectively. Expression increased dose-dependently from 9 to 15 Gy. In mice having an increased BUN level, 7 of 10 and 8 of 10 were positive for c-myc and c-fos, respectively. All 6 mice having an unchanged BUN level were negative for c-fos, while 5 were negative for c-myc. CONCLUSION: Measurement of c-myc and c-fos gene expression is potentially an early indicator of late radiation damage to the kidney.

Animals↗

PubMed1988

Transcriptional and posttranscriptional control of c-fos gene expression in human monocytes.

We examined the mechanisms that are responsible for the regulation of c-fos gene expression in human monocytes. Levels of c-fos mRNA were low or undetectable in resting monocytes. Results of run-on transcription assays, however, demonstrated that both the first two and last two exons of the c-fos gene were transcribed at similar rates, and that only the sense strand of this gene was transcribed. These findings suggest that the level of c-fos transcripts in resting human monocytes is controlled at a posttranscriptional level. Activation of resting monocytes with phorbol ester was associated with a rapid and transient increase in c-fos mRNA levels. This increase in c-fos transcripts was related to an enhanced rate of c-fos transcription. Moreover, exposure of resting monocytes to inhibitors of protein synthesis induced (i) a rapid and marked (300-fold) increase in c-fos mRNA levels, despite only a 9-fold increase in c-fos transcription, and (ii) a prolongation of the half-life of c-fos mRNA. Thus, while posttranscriptional control was responsible for the down-regulation of c-fos transcripts in both resting and activated human monocytes, transcriptional mechanisms were responsible for the transient increase in c-fos expression induced by phorbol ester. Furthermore, the marked increases in c-fos mRNA associated with inhibition of protein synthesis were regulated by both transcriptional and posttranscriptional mechanisms. These findings may be related to recent observations which indicate that both positive and negative factors transcriptionally regulate c-fos gene expression and that sequences found in the 3'-untranslated region of the c-fos mRNA are responsible for the stability of this transcript.

Cycloheximide↗

PubMed2002

C-fos gene expression induced in cells in specific hypothalamic structures by noxious mechanical stimulation and its [correction of it's] modification by exposure of the skin to extremely high frequency irradiation.

OBJECTIVES: The purpose of this study was to determine: 1) The spatial pattern of c-fos gene expression in rat hypothalamic neurons after exposure to NMS and 2) The expression of c-fos gene after combined exposure to NMS and EHF irradiation of the rat skin. METHODS: The experiments were performed on 28 male adult Sprague-Dawley rats. After rats were subjected to noxious mechanical stimulation (NMS) or its combination with EHF irradiation of the skin, cells in various hypothalamic structures were analyzed to determine theirs effects on c-fos gene expression, an accepted marker of the activation of neurons. C-Fos-like protein was revealed by an indirect immunoperoxidase method. RESULTS: This study revealed that NMS stimulates c-fos gene expression in the anterior hypothalamic nucleus (AHN), dorsomedial hypothalamic nucleus (DMH), ventromedial hypothalamic nucleus (VMH), and lateral hypothalamic area (LHA) by 157, 101, 199 and 115% respectively compared to control animals. Combined exposure to NMS and EHF irradiation directed at the skin in the region of the St36 acupuncture point projection site (left side) results in a decrease of the number of neurons that are activated in the AHN, DMH, VMH, and LHA by 33.6, 13.2, 31.0 and 32.9% respectively compared to the number of neurons activated by exposure to NMS by itself. EHF exposure of the skin of rats not subjected to NMS differentially effects the number of c-Fos positive cells expressed in hypothalamic structures: a decrease of 39.7% was observed in the number of activated neurons in the central part of LHA (level 28) compared to sham-irradiated animals, while an increase of 80.95% was noted in the number of c-Fos positive cells in the DMH compared to sham-irradiated animals. CONCLUSIONS: The spatial pattern and degree of activation of c-fos gene expression has been shown in cells of the hypothalamus of rats after exposure to NMS by itself and after NMS combined with EHF irradiation of the skin. The "stress" reaction of cells in specific hypothalamic structures has been shown to be decreased after EHF exposure of the skin.

Animals↗

PubMed2000

[Effects of zinc deficiency on the c-fos gene expression and transcription in the epiphyses of fetal mouse long bone in culture].

The effects of zinc on c-fos gene expression and transcription in the epiphyses of fetal long bone were studied in mice. The long bones of 16-day fetal mouse were cultured for 48 hours(in medium GBJb) and then used for measuring c-fos gene expression and transcription by immunohistochemistry and in situ hybridization. The result was analyzed by an imaged-analyses system. The experiment was divided into zinc control group(ZC), zinc deficiency group(ZD), zinc deficiency replenish group(ZDR) and zinc stimulatory group(ZS) respectively. The result showed that 1) zinc deficiency caused c-fos protein and mRNA expression and the number of reactive cell decreased. 2) when zinc concentration of medium was 100 mumol/L, the expression and transcription of c-fos gene were increased in hypertrophic, proliferative and resting zone of epiphyses. The research suggested that zinc could affect the expression of c-fos gene in mouse fetal long bone.

Animals↗

PubMed2001

Relationship between c-fos gene expression and delayed neuronal death in rat neonatal hippocampus following hypoxic-ischemic insult.

OBJECTIVE: To explore the mechanism of perinatal hypoxia-ischemia encephalopathy, we studied the expression of the c-fos gene and its relationship with delayed neuronal death in a rat model. METHODS: Cerebral hypoxia-ischemia was produced in 7-day-old SD rats using the Rice model. Reverse transcription PCR (RT-PCR), immunohistochemistry and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) were used to detect the expression of c-fos gene and cell apoptosis in the hippocampus. RESULTS: The selective expression of c-fos and delayed cell apoptosis were observed in the hypoxia-ischemia hippocampus. Expression of the c-fos gene was seen in the CA4 and cingulate sulcus neurons, and apoptosis was observed in the CA1 neurons. CONCLUSION: Transient expression of the c-fos gene may induce cerebral cell apoptosis, and may have complex relations with delayed cell death.

Animals↗

PubMed1998

Formoterol and isoproterenol induce c-fos gene expression in osteoblast-like cells by activating beta2-adrenergic receptors.

Formoterol, a beta2-adrenergic agonist has been shown in ovariectomized rat models to have anabolic effects on bone. However, those studies did not determine whether the effect of formoterol was by a direct action on bone cells themselves or indirectly via anabolic action on muscle. To address the question of whether formoterol could directly affect osteoblast function we investigated the expression patterns of beta3-adrenergic receptors (betaARs) in human osteoblast-like cells and functional coupling to gene expression. Northern blot analysis showed that betaAR subtypes are expressed at different levels in the osteoblast-like cell lines TE-85, SaOS-2, MG-63, and OHS-4. beta1AR expression was found in SaOS-2, OHS-4, and TE-85, but not MG-63 cells. beta2ARs are expressed at higher levels in MG-63 cells than in TE-85 and SaOS-2 cells, but were not detected in OHS-4 cells. PCR analysis paralleled the northern blot analysis except that beta3AR expression was found in one of three human primary osteoblast cDNAs tested. beta3AR expression was not found in any of the osteoblast-like cell lines. The nonspecific betaAR agonist, isoproterenol, and the beta2AR-specific agonist, formoterol, induced c-fos gene expression in cultured SaOS-2 cells in an immediate early fashion. This effect was inhibited by the beta2AR-specific antagonist, ICI 118551, but not by the beta1AR-specific antagonist, CGP 20712, indicating that induction of c-fos gene expression is specifically mediated by beta2ARs. c-fos gene expression was induced by both isoproterenol and formoterol via increases in cAMP, which in turn activated the cAMP/PKA pathway; the PKA inhibitor, H89, inhibited c-fos gene expression. Thus, betaARs are expressed in osteoblast-like cells and are coupled to c-fos gene expression via the beta2AR, increases in cAMP levels and activation of a PKA-dependent pathway.

Adrenergic beta-Agonists↗

PubMed2005

Inhibitory effect of trilinolein on endothelin-1-induced c-fos gene expression in cultured neonatal rat cardiomyocytes.

Trilinolein, isolated from the traditional Chinese herb Sanchi (Panax notoginseng), has been shown to have myocardial protective effects via its antioxidant ability. However, the cellular and molecular mechanisms of the protective effect of trilinolein in the heart remain to be elucidated. Oxidative mechanisms have been implicated in neonatal cardiomyocyte hypertrophy. We previously reported that ET-1 induces ROS generation via the ET(A) receptor and ROS modulates c-fos gene expression. We have therefore examined whether trilinolein attenuates ROS production and ET-1-induced c-fos gene expression in cardiomyocytes. Cultured neonatal rat cardiomyocytes were stimulated with ET-1 (10 nM), and c-fos gene expression was examined. Trilinolein (1 and 10 microM) inhibited ET-1-induced c-fos gene expression in cardiomyocytes. We also examined the effects of trilinolein on ET-1-increased NADPH oxidase activity and superoxide formation. Trilinolein inhibited ET-1-increased NADPH oxidase activity and superoxide formation in a concentration-dependent manner. This increase in superoxide production by ET-1 was significantly inhibited by trilinolein, diphenyleneiodonium, or N-acetylcysteine. Trilinolein also decreased ET-1- or H2O2-induced extracellular signal-regulated kinase (ERK) phosphorylation, c-Jun NH2-terminal kinase (JNK) phosphorylation, and activator protein-1 activation. These data indicate that trilinolein inhibits ET-1-induced ERK phosphorylation, JNK phosphorylation, and c-fos gene expression via attenuating superoxide production in cardiomyocytes.

Animals↗

PubMed1990

Induction of c-fos gene expression by arabinofuranosylcytosine in human KG-1 leukemia cells.

Previous studies have demonstrated that the c-fos proto-oncogene is expressed during induction of differentiation and as an immediate early response to growth factors. The present results demonstrate that exposure of human KG-1 myeloid leukemic cells to 1-beta-D-arabinofuranosylcytosine (ara-C) was associated with increases in c-fos gene expression. This effect was dependent on the concentration and time of ara-C treatment. The level of c-fos transcripts was maximal after 6 hr of exposure to 5 x 10(-6) M ara-C and subsequently declined to that in untreated cells. Nuclear run-on assays demonstrated low to undetectable levels of c-fos gene transcription in untreated KG-1 cells. In contrast, treatment with 5 x 10(-6) M ara-C for 6 hr was associated with increases in transcription of this gene. Although superinduction of c-fos expression has been observed at the post-transcriptional level in the presence of protein synthesis inhibition, this effect was not detectable in ara-C-treated KG-1 cells. These combined results demonstrate that ara-C increased c-fos mRNA levels in KG-1 cells and that this effect was associated with transcriptional activation of the c-fos gene.

Blotting, Northern↗

PubMed2003

Transient expression of E1A and Ras oncogenes causes downregulation of c-fos gene transcription in nontransformed REF52 cells.

Stable transformation of rat embryo fibroblast (REF) cells with E1A and cHa-ras oncogenes leads to downmodulation of c-fos gene transcription. This repression is provided in part by the association of Elk-1 transcription factor with histone deacetylases mediated through effects of Ras on MAP-kinase cascades. Here, we focus on the primary effects of E1A and Ras displayed in transient transfection assay on the transactivating capability of Elk-1, which is a key transcription factor of c-fos gene regulation. Our data show that E1A is able to suppress serum- and Ras-induced stimulation of Gal-luc reporter activity by a full-length Gal-Elk1-428 fusion protein as well as the expression of c-fos promoter-driven luciferase constructs (fos-luc). The repression can be relieved by trichostatin A, a histone deacetylase (HDAC) inhibitor, implying the involvement of HDACs and an inactive chromatin structure formed due to underacetylation of nucleosomal histones. Thus, upon transient transfection of E1A and Ras oncogenes in REF52 cells or their stable expression in E1A+cHa-ras cells, E1A contributes to the formation of inactive chromatin structure through association with p300/CBP histone acetyltransferases at c-fos promoters, whereas Ras mediates its effect through constitutive activation of the MAP/ERK kinase cascade, thereby promoting the recruitment of HDAC1 to the Elk-1 transcription factor. As a result, downregulation of c-fos gene transcription revealed in established E1A+Ras transformants is unlikely to be a consequence of cell transformation itself, but follows from primary effects of E1A and Ras on chromatin remodeling factors.

Adenovirus E1A Proteins↗