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PubMed1991

High-level expression of human c-jun gene causes cellular transformation of chicken embryo fibroblasts.

To analyze the transforming activity of c-jun, a Rous sarcoma virus (RSV) variant that carries human c-jun instead of v-src (JH1) was constructed. After infection onto chicken embryo fibroblasts (CEF), JH1 formed foci with a titer comparable to that of wild-type RSV, and the infected cells grew in soft agar, indicating that the human c-jun gene has transforming potential, like the v-jun gene. The expression of Fra-2, one of the recently isolated Fos-related antigens, but not Fos was detected in both JH1-infected CEF and CEF infected with the control retrovirus vector (DS3). Gel shift analysis using nuclear extracts from DS3-infected CEF revealed that the Fra-2/Jun complex contributes to the basal level of AP-1 DNA binding activity. A similar activity was detected in JH1-infected CEF, but these cells have an additional AP-1 binding activity derived from Jun homodimers that seems to play important roles in the cellular transformation.

Animals↗

PubMed1998

In vitro transcription of c-jun gene using fractionated nuclear extract from regenerating rat liver.

Regenerating rat liver serves as a source of proliferating cells, such a system can be used to study the regulation of genes involved in proliferation. We have established an in vitro transcription capable of supporting accurate transcription of cloned c-jun gene using fractionated nuclear extract prepared from partially hepatectomized rat liver. EcoR I linearized plasmid -132/+170 jun-CAT containing c-jun gene promoter region (-132 to +170 nucleotides) was transcribed in an in vitro run-off transcription assay and a transcript of expected size i.e. 370 nucleotides was obtained. The intensity of the transcript was dependent on the concentration of fractionated nuclear extract as well as template. The transcription was alpha-amanitin sensitive indicating that it is directed by RNA polymerase II.

Animals↗

PubMed1998

Transrepression of c-jun gene expression by the glucocorticoid receptor requires both AP-1 sites in the c-jun promoter.

The c-jun protooncogene encodes a nuclear protein, cJun, which is a major component of the AP-1 transcription factor. AP-1 regulates various aspects of cell proliferation and differentiation. As an immediate early response gene, the expression of the c-jun gene is affected by various extracellular stimuli, such as serum, phorbol esters, and glucocorticoids. In mouse L929 fibroblasts, dexamethasone (DEX) treatment caused a 60% reduction of c-jun mRNA levels. Previous studies indicated that this reduction is due to the alteration of the transcription rate of the c-jun gene. To further investigate the molecular mechanisms of transcriptional repression of c-jun by DEX, a full-length human c-jun promoter, from -1780 to +731, was amplified from genomic DNA using PCR and then linked to the luciferase reporter gene. To identify the regulatory elements responsible for the down-regulation, nested deletions spanning the promoter were generated, and the promoter/luciferase constructs were transiently transfected into L929 cells. Upon hormone treatment, basal activity of the full-length c-jun promoter was reduced by approximately 40%, which accounts for two-thirds of the overall down-regulation observed at the mRNA level. This reduction of c-jun promoter activity was abolished after deletion of the region between -1780 to -63, where two AP-1 sites (-182 and -64) are located. Site-directed deletion of these AP-1 sites reduced the basal activity of the c-jun promoter and prevented repression by DEX. Repression of the c-jun gene is due to the transrepression activity of the glucocorticoid receptor (GR), as determined using GR mutants lacking this activity. Overexpression of cJun overcame the negative effect of DEX, suggesting that down-regulation of the c-jun gene by hormone is mediated by the interaction between the GR and the cJun protein. These studies are the first to show that glucocorticoids can repress c-jun promoter activity through the AP-1 sites in the c-jun promoter in mouse fibroblast cells. They also suggest that inhibition of cell proliferation by glucocorticoids may be due not only to the interference with AP-1 activity on other cellular genes, but also because of a direct transcriptional suppression of c-jun gene expression by the GR.

Animals↗

PubMed1992

Involvement of reactive oxygen intermediates in the induction of c-jun gene transcription by ionizing radiation.

Previous work has demonstrated that the cellular response to ionizing radiation includes transcriptional activation of the c-jun gene. The signaling events responsible for this response, however, remain unclear. The present studies have examined the effects of ionizing radiation on c-jun expression in a variant of HL-60 cells, designated HL-525, which is deficient in protein kinase C (PKC)-mediated signal transduction. The results demonstrate that these cells express low levels of PKC alpha and PKC beta transcripts and exhibit an attenuated induction of c-jun expression following treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA). In contrast, HL-525 cells respond to ionizing radiation with an increase in c-jun mRNA which is more pronounced than that in wild-type HL-60 cells. These cells similarly respond to ionizing radiation with increased expression of the jun-B, jun-D, c-fos, and fos-B genes. Nuclear run-on assays demonstrate that X-ray-induced c-jun expression in HL-525 cells is regulated by increases in the rate of c-jun gene transcription. Moreover, mRNA stability studies in irradiated HL-525 cells demonstrate that the half-life of c-jun transcripts is prolonged compared to that in wild-type cells. Studies with N-acetyl-L-cysteine (NAC), an antioxidant, suggest that X-ray-induced transcriptional activation of the c-jun gene is mediated at least in part through the formation of reactive oxygen intermediates (ROIs). In this context, H2O2 also induced c-jun expression in HL-525 cells, and this effect was inhibited by NAC.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Nucleus↗

PubMed1998

Doxorubicin-induced alterations of c-myc and c-jun gene expression in rat glioblastoma cells: role of c-jun in drug resistance and cell death.

We studied the effect of doxorubicin on the expression of c-myc and c-jun in the rat glioblastoma cell line C6 and its doxorubicin-resistant variant C6 0.5, at equitoxic exposures. For quantitation, the mRNA levels of these oncogenes were related to those of two domestic genes, beta-actin and glyceraldehyde phosphate dehydrogenase. After a transient overexpression of the genes during the first hour of incubation, there was a selective, dose-dependent down-regulation of both genes by doxorubicin in the sensitive cells. In the resistant cell line, c-myc expression was also decreased in response to doxorubicin incubation, but the expression of c-jun remained unchanged over the whole range of concentrations. In contrast, vincristine had no effect on the amounts of c-myc and c-jun mRNAs in either line. The effect of doxorubicin on the mRNA levels of c-jun was also observed on the JUN proteins by immunoblotting, but the MYC protein levels remained unchanged upon doxorubicin treatment. There was a significant correlation between the levels of c-myc and c-jun gene expression and the degree of growth inhibition induced by doxorubicin. In addition, doxorubicin induced a fragmentation of DNA in sensitive cells, but not in resistant cells, thus revealing a resistance to apoptosis in this line. Doxorubicin-induced cell death did not appear to be mediated by p53 in either cell line.

Animals↗

PubMed2004

An association between ethanol-evoked enhancement of c-jun gene expression in the nucleus tractus solitarius and the attenuation of baroreflexes.

BACKGROUND: An increased expression of Fos, the protein product of the immediate early gene c-fos, in the nucleus tractus solitarius (NTS) is associated with dysfunction in baroreceptor reflex control of heart rate. Our previous studies demonstrated that ethanol attenuates baroreflex sensitivity (BRS) in rats and humans. In this study, we tested the hypothesis that enhanced expression of the immediate early gene c-jun (an index of neuronal activity) in the NTS contributes to the baroreflex dysfunction caused by ethanol. METHODS: Conscious male spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats were used to measure blood pressure, heart rate, and baroreflex sensitivity (Oxford method). The c-jun messenger RNA (mRNA) expression in NTS was measured by in situ hybridization. RESULTS: Ethanol elicited dose-dependent attenuation in BRS in WKY rats, which was associated with significant increases in c-jun mRNA in the NTS. In contrast, ethanol had no effect on BRS or c-jun mRNA in the NTS of the SHRs; the latter exhibited significantly lower BRS and higher c-jun mRNA in the NTS compared with WKY rats. CONCLUSIONS: An increased basal level of c-jun mRNA in the NTS may contribute to the reduced BRS in the SHR, and ethanol enhancement of neuronal activity of the NTS, expressed as increased c-jun mRNA expression, may contribute to its attenuation of BRS, which highlights the NTS as a neuroanatomical target for ethanol action on baroreflexes.

Animals↗

PubMed1990

Regulation of c-jun gene expression by cAMP in HL-60 myeloid leukemia cells.

Previous studies have demonstrated that expression of the c-jun proto-oncogene is induced by phorbol esters and other agents that activate protein kinase C. The present work has examined the involvement of cAMP-dependent signaling mechanisms in the regulation of c-jun gene expression. Low levels of c-jun transcripts were detectable in untreated HL-60 myeloid leukemia cells. In contrast, treatment of these cells with 8-bromoadenosine 3',5'-cyclic monophosphate was associated with increases in c-jun expression that were maximal at 3 h and then declined to pretreatment levels. Similar findings were obtained with N6,2'-O-dibutyryladenosine 3',5'-cyclic monophosphate and 8-(4-chlorophenylthio)-adenosine 3',5'-cyclic monophosphate, but not with 8-bromoguanosine 3',5'-cyclic monophosphate. c-jun transcripts were also increased with agents, such as prostaglandin E2 and forskolin, that increase intracellular cAMP levels. The effects of these agents on c-jun expression were associated with activation of cAMP-dependent protein kinase. Moreover, inhibition of this kinase activity with the isoquinolinesulfonamide derivative H8 was associated with a block in the induction of c-jun expression by cAMP. Nuclear run-on analysis further demonstrated that while c-jun transcription is a low levels in untreated HL-60 cells, treatment with cAMP analogs is associated with an increase in the transcriptional rate of this gene. Taken together, these findings suggested that, in addition to activation of protein kinase C, stimulation of cAMP-dependent protein kinase activity is also involved in the transcriptional induction of c-jun gene expression. The present results similarly demonstrate that c-fos gene transcription is induced in HL-60 cells through a mechanism involving cAMP-dependent protein kinase activity. Since heterodimers of the Jun and Fos proteins have been shown to bind to the phorbol ester-responsive element (AP-1-binding site), the present findings indicate that cAMP-induced signaling events may also regulate gene transcription through formation of Fos/Jun heterodimers and that interaction between phorbol ester- and cAMP-dependent pathways could occur through induction of the c-jun gene in these cells.

Blotting, Northern↗

PubMed1989

jun-D: a third member of the jun gene family.

The protooncogene c-jun encodes a component of the transcription factor AP-1. Both murine c-jun and a related gene (jun-B) are rapidly activated in BALB/c3T3 cells by serum growth factors. We report here the cloning and analysis of a cDNA encoding a third member of the murine jun family, jun-D. The amino acid sequence encoded by jun-D has two extensive regions of homology with the other Jun proteins. One homology region includes the DNA-binding domain and sequences required for dimer formation and interaction with the Fos oncoprotein; the other includes the acidic sequence thought to be involved in gene activation. All three jun mRNAs are present in a variety of murine tissues and cell lines. In resting 3T3 cells, jun-D is expressed at a higher level compared to c-jun and jun-B, and its transcription is stimulated only slightly by serum growth factors. Thus, jun-D appears to be regulated differently than c-jun and jun-B.

Amino Acid Sequence↗

PubMed2000

Signal Transduction in TNF-alpha-induced c-jun Gene Expression.

Our previous studies demonstrated that p38 mitogen-activated protein (MAP) kinase regulated the c-jun protein expression through phosphorylation of transcription factors of myocyte enhancer factors 2 (MEF2) family. There was a MEF2 binding site in the promoter of c-jun gene. Members of the MEF2 family of trans-cription factors bound as homo- and heterodimers to this MEF2 binding site. Here the potential role of the p38 and BMK1 MAP kinases in the regulation of c-jun expression induced by TNF-alpha was examined. It was shown that p38 MAP kinase up-regulated the transcription activity of MEF2A, while BMK1 MAP kinase up-regulated not only the transcription activity of MEF2A, but also MEF2D. The p38 and BMK1 MAP kinases had coordinated effect on the regulation of c-jun transcription. TNF-alpha induced the formation of MEF2A/MEF2D hete-rodimer. Over-expression of homodimer of MEF2 proteins inhibited c-jun transcription induced by TNF-alpha, while over-expression of heterodimer MEF2A/MEF2D enhanced c-jun transcription induced by TNF-alpha. Phosphorylation of MEF2A and MEF2D by p38 and BMK1 respectively appeared very important in TNF-alpha induced MEF2A/MEF2D heterodimer formation to enhance c-jun gene expression.

Journal Article↗

PubMed1999

Arachidonic acid induces mobilization of calcium stores and c-jun gene expression: evidence that intracellular calcium release is associated with c-jun activation.

Arachidonic acid (AA) plays a signaling role in the induction of several genes. We previously demonstrated that AA induces c-jun gene expression in the stromal cell line +/+.1 LDA 11 by a signaling pathway involving activation of the c-jun amino-terminal kinase (JNK). This study investigated the role of calcium in AA signaling of c-jun activation in +/+.1 LDA 11 cells. AA (10-50 microM) caused a rapid dose-dependent rise in cytosolic calcium. AA-induced calcium mobilization involved both influx of extracellular calcium and the release of intracellular calcium. The importance of calcium was investigated by variation of the extracellular calcium concentration, chelation of intracellular calcium and by calcium ionophore-induced influx of extracellular calcium. AA-induced c-jun gene expression and increased luciferase activity of a construct containing the high affinity AP-1 binding site was decreased in cells preincubated with the intracellular calcium chelator 1,2-bis(o-aminophenoxy)-eThane-N,N,N',N',-tetraacetic acid tetra(aceToxymethyl-esTer) (BAPTA-AM, 10 microM) prior to stimulation with AA. Similarly, chelation of intracellular calcium decreased AA-induced JNK activation. On the contrary, changes in the extracellular calcium concentration had no effect. Also, ionophore A23187 failed to induce c-jun and JNK activation either alone than in combination with AA. These results suggested that calcium was required for AA-dependent activation of c-jun, but that calcium alone was insufficient to induce activation of c-jun. Thus, release of calcium from intracellular stores is implicated in the signaling pathway of AA-induced c-jun activation in stromal cells.

Arachidonic Acid↗

PubMed1992

Transcriptional regulation of the c-jun gene by retinoic acid and E1A during differentiation of F9 cells.

Differentiation of mouse F9 embryonal carcinoma (EC) cells can be induced by exposure to retinoic acid (RA) or by expression of adenovirus E1A. The transcription of the c-jun gene is stimulated by either RA or E1A. We report here that both RA and E1A strongly induce the expression of chloramphenicol acetyltransferase (CAT) from c-jun promoter/CAT reporter construct (c-jun/CAT), which is stably integrated into F9 cells, in a manner that is independent of both copy number and integration locus. The induction of c-jun/CAT expression is observed in undifferentiated F9 cells, but not in differentiated F9 cells, adenovirus-infected F9 cells or HeLa cells. Deletion analysis of the promoter region of the c-jun gene indicates that the sequence elements required for the RA- and E1A-mediated induction are identical and they have been defined as a region of 145 bp between -190 and -46 of the 5' flanking region of c-jun. This RA and E1A response element (RERE) contains five variants of the motif CGCGGTGACGNT. The upstream two motifs are adjacent and extend in opposite directions, creating an imperfect palindrome. The downstream four motifs are located at 35 or 36 bp intervals in the same orientation. Substitution and insertion analysis indicates that these motifs and their regular intervals are important for the activity of the RERE.

Adenoviruses, Human↗

PubMed1992

Ultraviolet-radiation induced c-jun gene transcription: two AP-1 like binding sites mediate the response.

In HeLa cells transcription of the c-jun gene is activated strongly and rapidly by ultraviolet (UV) irradiation and, to a somewhat lesser extent, by treatment with phorbol ester tumor promoters. In the same cells UV and phorbol esters only marginally enhance the abundance of RNA transcribed from the jun D gene and from the gene coding for the serum response factor (which in turn acts on the UV and phorbol ester response element of the c-fos gene). In contrast to c-jun, jun B transcription is induced more efficiently by phorbol ester than by UV irradiation, suggesting that the members of the jun family are differently regulated. The promoter of c-jun carries two enhancer elements resembling AP-1 binding sites: the jun1 UV response element (URE-71 TGACATCA -64) and the jun2 URE (-190 TTACCTCA-183). These elements act independently in the UV induced expression of c-jun. In the context of the complete c-jun promoter they seem not to be required for c-jun induction by phorbol esters. When fused to the Herpes simplex thymidine kinase promoter, however, the isolated elements mediate induction by both UV and phorbol esters. UV and phorbol ester treatment of cells increases the binding of transcription factors to both elements. Both elements bind factors different in modification or/and constitution from AP-1, the heterodimeric transcription factor composed of c-Fos and c-Jun that controls the activity of the UV and phorbol ester response element (-72 TGAGTCA-66) of the human collagenase gene.

Base Sequence↗

PubMed2004

Effects of the histone deacetylase inhibitor trichostatin A on nuclear texture and c-jun gene expression in drug-sensitive and drug-resistant human H69 lung carcinoma cells.

BACKGROUND: Texture analysis of chromatin patterns by image cytometry can be used in the development and refinement of diagnosis and prognosis of cancers and in the follow-up of therapies. However, little is known about the biological mechanisms underlying these patterns. Epigenetic mechanisms as histone posttranslational modifications and particularly histone acetylation could play a major role in the determination of these chromatin patterns and then influence nuclear texture measurements. METHODS: This study examined the consequences of treatment by the histone deacetylase inhibitor trichostatin A (TSA) on the nuclear texture in human cell lines sensitive and resistant to chemotherapy. Small cell lung carcinoma H69 cells and their variant H69-VP, which is resistant to etoposide, were incubated with 100 ng/ml of TSA for 0 to 24 h. Nuclear texture was evaluated by image cytometry and compared with the histone H4 acetylation level measured by western blotting and expression of c-jun gene evaluated by reverse transcription and real-time polymerase chain reaction. RESULTS: TSA treatment induced an increase in histone H4 acetylation level in both cell lines. However, at the level of chromatin texture, sensitive H69 cells displayed a progressive chromatin decondensation up to 24 h, whereas resistant H69-VP showed rapid (8 h) but transient changes. Similarly, expression of c-jun increased regularly in TSA-treated H69 cells. In H69-VP cells, an increase was also observed up to 12 h followed by a decrease after 24 h of treatment. CONCLUSIONS: Analysis of nuclear texture appeared to be a sensitive technique to detect chromatin pattern alterations induced by the histone deacetylase inhibitor TSA in the H69 cell line and enabled the observation of chromatin pattern discrepancies between chemotherapeutic drug-sensitive and drug-resistant cells during this treatment. When c-jun gene expression was analyzed as gene sensitive to epigenetic control, these textural differences seemed to be correlated to gene expression.

Carcinoma, Small Cell↗

PubMed1995

Activation of multiple transcription factors and fos and jun gene family expression in cells exposed to a single electric pulse.

We report that exposure of cells to a single electric pulse (250-1250 V/cm) results in the rapid and persistent activation of the DNA binding activities of a number of transcription factors, including AP-1, SP1, AP-2, and NF-kappa B, and the transient expression of select members of the fos and jun gene families. Induction of gene expression occurs primarily at the level of transcription, although c-jun expression also appears to be regulated posttranscriptionally. Interestingly, maximal induction of gene expression is detected at electrical field strengths that do not result in pore formation in the plasma membrane and that do not significantly affect cell viability. Exposure of cells to electric pulses does not result in the activation of HSF1 DNA binding activity, or the induction of hsp70 or p53 protein synthesis, indicating that the induction of fos and jun gene expression is not coincident with protein or DNA damage. The results of these studies suggest that electrical pulses may represent a novel mechanism for inducing the activities of multiple transcription factors and the expression of select members of the fos and jun gene families.

3T3 Cells↗

PubMed1991

Rapid and preferential activation of the c-jun gene during the mammalian UV response.

Exposure of mammalian cells to DNA-damaging agents leads to activation of a genetic response known as the UV response. Because several previously identified UV-inducible genes contain AP-1 binding sites within their promoters, we investigated the induction of AP-1 activity by DNA-damaging agents. We found that expression of both c-jun and c-fos, which encode proteins that participate in formation of the AP-1 complex, is rapidly induced by two different DNA-damaging agents: UV and H2O2. Interestingly, the c-jun gene is far more responsive to UV than any other immediate-early gene that was examined, including c-fos. Other jun and fos genes were only marginally affected by UV or H2O2. Furthermore, UV is a much more efficient inducer of c-jun than phorbol esters, the standard inducers of c-jun expression. This preferential response of the c-jun gene is mediated by its 5' control region and requires the TPA response element, suggesting that this element also serves as an early target for the signal transduction pathway elicited by DNA damage. Both UV and H2O2 lead to a long-lasting increase in AP-1 binding activity, suggesting that AP-1 may mediate the induction of other damage-inducible genes such as human collagenase.

DNA-Binding Proteins↗

PubMed2004

Dominant-negative mutant of c-Jun gene transfer: a novel therapeutic strategy for colorectal cancer.

Activator protein-1 (AP-1), a transcription factor, is activated through many oncogenic signals. However, its biological role in colorectal cancer has not been fully elucidated. To investigate the role of AP-1 in colorectal cancer, we constructed an adenovirus-expressing TAM67, a dominant-negative mutant of c-Jun lacking the transactivation domain of wild c-Jun (DN-c-Jun), to inhibit endogenous AP-1. AP-1 DNA-binding activity was increased in colon cancer cells (HT-29 cells) by serum stimulation, followed by an increase in both [(3)H]thymidine incorporation and cell number. Transfection of Ad-DN-c-Jun to HT-29 cells significantly inhibited serum-induced cell proliferation in vitro. As shown by flow cytometric analysis, DN-c-Jun significantly inhibited entrance into S phase after serum stimulation, thereby leading to G(1) arrest. In vivo transfection of Ad-DN-c-Jun into xenografted HT-29 cell tumors in nude mice significantly decreased tumor volume on day 21 after treatment. A change was associated with decrease in Ki-67 labeling index. These observations together showed that AP-1 is a critical modulator for proliferation and cell cycle of HT-29 cells. We obtained the first evidence that DN-c-Jun gene transfer exerted a significant antitumor effect on colon cancer both in vitro and in vivo. DN-c-Jun gene transfer may be a new candidate for treatment of colorectal cancer.

Animals↗

PubMed2005

Selective regulation of c-jun gene expression by mitogen-activated protein kinases via the 12-o-tetradecanoylphorbol-13-acetate- responsive element and myocyte enhancer factor 2 binding sites.

To further understand how the mitogen-activated protein kinase (MAPK) signaling pathways regulate AP-1 activity, we have elucidated the physiological role of these cascades in the regulation of c-jun gene expression. c-Jun is a crucial component of AP-1 complexes and has been shown in vitro to be a point of integration of numerous signals that can differentially affect its expression as well as its transcriptional activity. Our strategy was based on the use of (i) genetically modified fibroblasts deficient in components of the MAPK cascades and (ii) pharmacological reagents. The results demonstrate that c-Jun NH(2)-terminal protein kinase (JNK) is essential for a basal level of c-Jun expression and for c-Jun phosphorylation in response to stress. In addition to JNK, p38 MAPK or ERK1/2 and ERK5 are required for mediating UV radiation- or epidermal growth factor (EGF)-induced c-Jun expression, respectively. Further studies indicate that p38 MAPK inhibits the activation of JNK in response to EGF, causing a down-regulation of c-Jun. Overall, these data provide important insights into the mechanisms that ultimately determine the function of c-Jun as a regulator of cell fate.

Animals↗

PubMed1990

Transcriptional regulation of c-jun gene expression by arabinofuranosylcytosine in human myeloid leukemia cells.

Previous studies have demonstrated that 1-beta-D-arabinofuranosylcytosine (ara-C) induces terminal differentiation of human myeloid leukemia cells. Other studies have shown that the c-jun protooncogene is expressed during phorbol ester-induced myeloid differentiation. This work examines the effects of ara-C on c-jun gene expression in human KG-1 myeloid leukemia cells. The results demonstrate that c-jun transcripts are undetectable in uninduced KG-1 cells and that ara-C induces expression of this gene in a concentration- and time-dependent manner. Ara-C treatment was also associated with increases in c-jun transcripts in U-937, THP-1, and HL-60 myeloid leukemia cells. Furthermore, transcriptional run-on analysis has demonstrated that exposure to ara-C increases the rate of c-jun gene transcription. The results also demonstrate that while inhibition of protein synthesis superinduces c-jun mRNA levels in phorbol ester-treated KG-1 cells, cycloheximide had no effect on the induction of c-jun transcripts during ara-C treatment. Moreover, the half-life of c-jun transcripts in ara-C-treated KG-1 cells was 42 min. These findings suggest that the increase in c-jun mRNA observed during ara-C treatment is regulated by a transcriptional mechanism, and that c-jun may be involved in the induction of differentiation and regulation of gene expression by ara-C.

Actins↗