Multiple signaling pathways control the activation of the CEF-4/9E3 cytokine gene by pp60(v-src)

Bojana Bojović, Natalie Rodrigues, Mohammed Dehbi, Pierre André Bédard

Research output: Contribution to journalArticle

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Abstract

The CEF-4/9E3 cytokine gene is expressed aberrantly in chicken embryo fibroblasts (CEF) transformed by the Rous sarcoma virus. The expression of CEF-4 is dependent on both transcriptional and post-transcriptional mechanisms of regulation. The characterization of the promoter region indicated that three distinct regulatory elements corresponding to an AP-1 binding site (or TRE), a PRDIL/κB domain, and a CAAT box are involved in the activation by pp60(varc). In this report we investigate the signaling pathways controlling the expression of the TRE and PRDII domain. The expression of a dominant negative mutant of p21(ras) reduced the activity of both elements. In contrast a similar mutant of c-Raf-1 affected modestly the activation dependent on the TRE but not PRDII. The stress-activated protein kinase (SAPK)/Jun N-terminal kinase (JNK) pathway was important for the activity of PRDII and the TRE but was not markedly stimulated by pp60(v- arc). The addition of calphostin C and the inhibition of protein kinase C (PKC) diminished the accumulation of the CEF-4 mRNA and reduced the activity of a TRE-controlled promoter. Likewise, the depletion of PKC by chronic treatment with phorbol esters inhibited the activation of the TRE. Rous sarcoma virus-transformed CEF treated with calphostin C were also flatter, did not display a high degree of criss-crossing, and appeared morphologically normal. Hence PKC was important for the activation of AP-1 and the morphological transformation of CEF. The constitutive expression of CEF-4 was correlated with transformation only when dependent on the TRE. This was not true for PRDII, which was the only element required for the constitutive activation to the CEF-4 promoter in nontransformed cells treated chronically with phorbol esters.

Original languageEnglish
Pages (from-to)22528-22537
Number of pages10
JournalJournal of Biological Chemistry
Volume271
Issue number37
DOIs
Publication statusPublished - 25 Sep 1996
Externally publishedYes

Fingerprint

Oncogene Protein pp60(v-src)
Fibroblasts
Chickens
Embryonic Structures
Genes
Chemical activation
Cytokines
Protein Kinase C
Rous sarcoma virus
Transcription Factor AP-1
Phorbol Esters
Viruses
Proto-Oncogene Proteins p21(ras)
Heat-Shock Proteins
Genetic Promoter Regions
Protein Kinases
Phosphotransferases
Binding Sites

ASJC Scopus subject areas

  • Biochemistry

Cite this

Multiple signaling pathways control the activation of the CEF-4/9E3 cytokine gene by pp60(v-src). / Bojović, Bojana; Rodrigues, Natalie; Dehbi, Mohammed; Bédard, Pierre André.

In: Journal of Biological Chemistry, Vol. 271, No. 37, 25.09.1996, p. 22528-22537.

Research output: Contribution to journalArticle

Bojović, Bojana ; Rodrigues, Natalie ; Dehbi, Mohammed ; Bédard, Pierre André. / Multiple signaling pathways control the activation of the CEF-4/9E3 cytokine gene by pp60(v-src). In: Journal of Biological Chemistry. 1996 ; Vol. 271, No. 37. pp. 22528-22537.
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abstract = "The CEF-4/9E3 cytokine gene is expressed aberrantly in chicken embryo fibroblasts (CEF) transformed by the Rous sarcoma virus. The expression of CEF-4 is dependent on both transcriptional and post-transcriptional mechanisms of regulation. The characterization of the promoter region indicated that three distinct regulatory elements corresponding to an AP-1 binding site (or TRE), a PRDIL/κB domain, and a CAAT box are involved in the activation by pp60(varc). In this report we investigate the signaling pathways controlling the expression of the TRE and PRDII domain. The expression of a dominant negative mutant of p21(ras) reduced the activity of both elements. In contrast a similar mutant of c-Raf-1 affected modestly the activation dependent on the TRE but not PRDII. The stress-activated protein kinase (SAPK)/Jun N-terminal kinase (JNK) pathway was important for the activity of PRDII and the TRE but was not markedly stimulated by pp60(v- arc). The addition of calphostin C and the inhibition of protein kinase C (PKC) diminished the accumulation of the CEF-4 mRNA and reduced the activity of a TRE-controlled promoter. Likewise, the depletion of PKC by chronic treatment with phorbol esters inhibited the activation of the TRE. Rous sarcoma virus-transformed CEF treated with calphostin C were also flatter, did not display a high degree of criss-crossing, and appeared morphologically normal. Hence PKC was important for the activation of AP-1 and the morphological transformation of CEF. The constitutive expression of CEF-4 was correlated with transformation only when dependent on the TRE. This was not true for PRDII, which was the only element required for the constitutive activation to the CEF-4 promoter in nontransformed cells treated chronically with phorbol esters.",
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