Transcription factor ATF3 partially transforms chick embryo fibroblasts by promoting growth factor-independent proliferation

Perez, Sandrine; Vial, Emmanuel; Dam, Hans van; Castellazzi, Marc

doi:10.1038/sj.onc.1204200

Cited by 59 publications

(46 citation statements)

References 42 publications

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“…The resulting cells display a typical, fusiform morphology and show enhanced proliferation in medium with reduced amounts of serum. However, rat ATF3-overexpressing CEFs do not e ciently grow in soft agar, thereby resembling CEFs transformed by the ATF2-preferring mutant Jun-m1 (Perez et al, 2001). This indicates that ATF3, a potential target gene of Jun : ATF2 in mammalian cells (Figure 1), has similar e ects as Jun : ATF2 on CEFs.…”

Section: Partial Transformation Of Cefs By Atf3mentioning

confidence: 79%

“…As the partial transformed phenotype induced by ATF3 (serum-independent but no anchorage-independent proliferation) is strikingly similar to the (partial) transformed phenotype induced by v-Jun-m1 (Perez et al, 2001), it was examined whether ATF3 and v-Jun(-m1) have similar e ects on CEF gene expression. These studies showed that v-Jun target genes can be divided in three di erent groups.…”

Section: Repression Of Cellular Genes By Atf3 In Cefsmentioning

confidence: 99%

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Distinct roles of Jun : Fos and Jun : ATF dimers in oncogenesis

2001

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Section: Partial Transformation Of Cefs By Atf3mentioning

confidence: 79%

Section: Repression Of Cellular Genes By Atf3 In Cefsmentioning

confidence: 99%

Distinct roles of Jun : Fos and Jun : ATF dimers in oncogenesis

2001

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“…This could allow c-Myc in cooperation with ATF2 to regulate transcription of such genes as ATF3 that are important for Rasmediated transformation but do not contain E-boxes. Identification of Atf3 as a Ras transformationsupporting gene is in line with its known oncogenic function that involves its ability to transform chick embryo fibroblasts (Perez et al, 2001). Moreover, overexpression of ATF3 leads to mammary tumor formation in mice (Wang et al, 2008).…”

Section: Atf2 and C-myc Co-operation In Ras Transformationmentioning

confidence: 83%

Identification of a c-Jun N-terminal kinase-2-dependent signal amplification cascade that regulates c-Myc levels in ras transformation

et al. 2011

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Ras is one of the most frequently activated oncogenes in cancer. Two mitogen-activated protein kinases (MAPKs) are important for ras transformation: extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase 2 (JNK2). Here we present a downstream signal amplification cascade that is critical for ras transformation in murine embryonic fibroblasts. This cascade is coordinated by ERK and JNK2 MAPKs, whose Rasmediated activation leads to the enhanced levels of three oncogenic transcription factors, namely, c-Myc, activating transcription factor 2 (ATF2) and ATF3, all of which are essential for ras transformation. Previous studies show that ERK-mediated serine 62 phosphorylation protects c-Myc from proteasomal degradation. ERK is, however, not alone sufficient to stabilize c-Myc but requires the cooperation of cancerous inhibitor of protein phosphatase 2A (CIP2A), an oncogene that counteracts protein phosphatase 2A-mediated dephosphorylation of c-Myc. Here we show that JNK2 regulates Cip2a transcription via ATF2. ATF2 and c-Myc cooperate to activate the transcription of ATF3. Remarkably, not only ectopic JNK2, but also ectopic ATF2, CIP2A, c-Myc and ATF3 are sufficient to rescue the defective ras transformation of JNK2-deficient cells. Thus, these data identify the key signal converging point of JNK2 and ERK pathways and underline the central role of CIP2A in ras transformation.

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“…Most of the biological functions of decorin are mediated by the protein core's unique organization of 10 tandem leucine-rich repeats (LRR) 1 which fold into an arch-shaped structure (9) whose concave surface is well suited to bind both globular and nonglobular proteins (2,10,11) as well as metal ions (12). Decorin expression is markedly suppressed in most transformed cells derived from primary malignant tumors (13)(14)(15) or in cells transformed by oncogenes such as vSrc (16), vJun (17), and ATF3 (18). On the contrary, decorin expression is markedly up-regulated during quiescence (19,20), and its levels can reach ϳ40-fold in post-confluent fibroblasts (21).…”

mentioning

confidence: 99%

Decorin Binds to a Narrow Region of the Epidermal Growth Factor (EGF) Receptor, Partially Overlapping but Distinct from the EGF-binding Epitope

Santra¹,

Reed²,

Iozzo

2002

Journal of Biological Chemistry

210

160

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Decorin, a small leucine-rich proteoglycan, is a key regulator of tumor growth by acting as an antagonist of the epidermal growth factor receptor (EGFR) tyrosine kinase. To search for cell surface receptors interacting with decorin, we generated a decorin/alkaline phosphatase chimeric protein and used it to screen a cDNA library by expression cloning. We identified two strongly reactive clones that encoded either the full-length EGFR or its ectodomain. A physiologically relevant interaction between decorin and EGFR was confirmed in the yeast two-hybrid system and further validated by experiments using EGF/EGFR interaction and transient cell transfection assays. Using a panel of deletion mutants, decorin binding was mapped to a narrow region of the EGFR within its ligand-binding L2 domain. Moreover, the central leucine-rich repeat 6 of decorin was required for interaction with the EGFR. Site-directed mutagenesis of the EGFR L2 domain showed that a cluster of residues, His 394 -Ile 402 , was essential for both decorin and EGF binding. In contrast, K465, previously shown to be cross-linked to epidermal growth factor (EGF), was required for EGF but not for decorin binding. Thus, decorin binds to a discrete region of the EGFR, partially overlapping with but distinct from the EGF-binding domain. These findings could lead to the generation of protein mimetics capable of suppressing EGFR function.Decorin, a prototype member of an expanding family of small leucine-rich proteoglycans (1), plays pivotal roles in modulating matrix assembly (2-5) and cell proliferation (6 -8). Most of the biological functions of decorin are mediated by the protein core's unique organization of 10 tandem leucine-rich repeats (LRR) 1 which fold into an arch-shaped structure (9) whose concave surface is well suited to bind both globular and nonglobular proteins (2, 10, 11) as well as metal ions (12). Decorin expression is markedly suppressed in most transformed cells derived from primary malignant tumors (13-15) or in cells transformed by oncogenes such as vSrc (16), vJun (17), and ATF3 (18). On the contrary, decorin expression is markedly up-regulated during quiescence (19,20), and its levels can reach ϳ40-fold in post-confluent fibroblasts (21). We have previously shown that decorin expression is enhanced around invasive carcinomas (22) and have proposed that decorin might represent a natural antagonist to the growing cancer cells (1). This working hypothesis is corroborated by the established effects of decorin on growth factor-mediated tumor progression (23, 4) and by its profound cytostatic effects on a wide variety of tumor cell lines (13,14,24,25). Lack of decorin is permissive for tumor development insofar as bitransgenic mice, lacking both decorin and the tumor suppressor p53, develop an accelerated lymphoma tumorigenesis (26). These earlier reports have been supported by the recent observation that decorin gene expression is differentially down-regulated in hepatocellular (27) and ovarian (28) carcinomas vis á vis their normal counter...

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Transcription factor ATF3 partially transforms chick embryo fibroblasts by promoting growth factor-independent proliferation

Cited by 59 publications

References 42 publications

Distinct roles of Jun : Fos and Jun : ATF dimers in oncogenesis

Distinct roles of Jun : Fos and Jun : ATF dimers in oncogenesis

Identification of a c-Jun N-terminal kinase-2-dependent signal amplification cascade that regulates c-Myc levels in ras transformation

Decorin Binds to a Narrow Region of the Epidermal Growth Factor (EGF) Receptor, Partially Overlapping but Distinct from the EGF-binding Epitope

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