Cell Transformation by the v-myc Oncogene Abrogates c-Myc/Max-mediated Suppression of a C/EBPβ-dependent Lipocalin Gene

Hartl, Markus; Matt, Theresia; Schuler, Wolfgang; Siemeister, Gerd; Kontaxis, Georg; Kloiber, Karin; Konrat, Robert; Bister, Klaus

doi:10.1016/j.jmb.2003.08.018

Cited by 18 publications

(43 citation statements)

References 79 publications

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“…The analyses clearly revealed association of p110 gagÀmyc with C/EBP proteins in MC29-transformed cells (Figure 5f), confirming and extending previous circumstantial evidence for possible direct interaction between these proteins (Mink et al, 1996;Hartl et al, 2003).…”

Section: Ws5 a Direct Transcriptional Target Of Myc F Reiter Et Alsupporting

confidence: 87%

“…These results were confirmed and extended by chromatin immunoprecipitation (ChIP) using chromatin from Q8 cells transformed by the MC29 p110 Gag-Myc hybrid protein (Bister et al, 1977) and containing high levels of WS5 mRNA (see Figure 1). Antisera directed against Myc, Gag or Max revealed binding of p110 gagÀmyc and Max to the WS5 promoter fragment containing the E-box cluster and the adjacent C/EBPa-binding site (Figure 4c), in agreement with the direct demonstration of p110 gagÀmyc -Max complexes in MC29-transformed cells (Hartl et al, 2003). Interestingly, antiserum directed against C/EBPa revealed binding of this transcription factor to the WS5 promoter fragment (Figure 4c), suggesting a functional role for the C/EBPabinding site flanking the E-box cluster (see Figure 2).…”

Section: Specific Binding Of Myc Max and C/ebpa To The Ws5 Promotersupporting

confidence: 82%

“…Hence, the quail WS5 coding sequence was inserted into the replicationcompetent retroviral RCAS vector, and the RCAS-WS5 construct was transfected into QEF and CEF. The empty vector and the RCAS-MC29 vector (Hartl et al, 2003) were used as controls. Ectopic expression of WS5 in cultured cells led to morphological alterations, more pronounced in QEF than in CEF (Figure 6a and c).…”

Section: Ws5 a Direct Transcriptional Target Of Myc F Reiter Et Almentioning

confidence: 99%

“…C/EBPa is a multifunctional transcription factor that is involved in the specification of the differentiated phenotype through gene activation, but was recently also implicated in the acceleration of cell proliferation and activation of metastasis related genes (Heckman et al, 2003;Liu et al, 2004;Wang and Timchenko, 2005). Notably, functional interactions of Myc with the C/EBPb protein have been reported previously (Mink et al, 1996;Hartl et al, 2003).…”

Section: Ws5 a Direct Transcriptional Target Of Myc F Reiter Et Almentioning

confidence: 99%

“…The following established lines of transformed QEF (Bister et al, 1977;Hartl et al, 2003) were used: VJ, transformed by ASV17 v-jun; Q8, transformed by MC29 v-myc; R(-)3, transformed by RSV v-src; and QT6, derived from a methylcholanthrene-induced fibrosarcoma. The quail cell lines Q/tM ON and Q/d3 conditionally transformed by doxycyclinedependent v-myc or v-jun alleles, and the retroviral construct RCAS-MC29 have been described (Oberst et al, 1999;Bader et al, 2000;Hartl et al, 2003). For construction of RCAS-WS5, a cDNA fragment containing the entire WS5 coding region was ligated into the ClaI site of the RCAS-BP vector.…”

Section: Cells and Retrovirusesmentioning

confidence: 99%

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WS5, a direct target of oncogenic transcription factor Myc, is related to human melanoma glycoprotein genes and has oncogenic potential

et al. 2006

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We have isolated a gene (WS5) that is specifically expressed at the mRNA and protein level in avian fibroblasts transformed by the v-myc oncogene of avian acute leukemia virus MC29. In a conditional cell transformation system, WS5 gene expression was tightly correlated with v-myc activation. The WS5 gene contains 11 exons, encoding a 733-amino acid protein with a transmembrane region and a polycystic kidney disease (PKD) domain. Near the transcriptional start site, the WS5 promoter contains a cluster of four binding sites for the Myc-Max complex and a binding site for transcription factor C/EBPa. Electrophoretic mobility shift assays and chromatin immunoprecipitation showed that Myc, Max and C/EBPa bind specifically to these sites. Functional promoter analyses revealed that both the Myc-binding site cluster and the C/EBPa-binding site are essential for strong transcriptional activation, and that Myc and C/EBPa synergistically activate the WS5 promoter. Ectopic expression of WS5 led to cell transformation documented by anchorage-independent growth. The human melanoma antigen Pmel17, a type I transmembrane glycoprotein, is the mammalian protein with the highest amino acid sequence identity (38%) to WS5. The Pmel17 gene is regulated by the MITF protein, a bHLHZip transcription factor with DNA binding specificities similar to those of Myc/Max. WS5 is also related to human glycoprotein GPNMB expressed in metastatic melanoma cells and implicated in the progression of brain and liver tumors.

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Section: Ws5 a Direct Transcriptional Target Of Myc F Reiter Et Alsupporting

confidence: 87%

Section: Specific Binding Of Myc Max and C/ebpa To The Ws5 Promotersupporting

confidence: 82%

Section: Ws5 a Direct Transcriptional Target Of Myc F Reiter Et Almentioning

confidence: 99%

Section: Ws5 a Direct Transcriptional Target Of Myc F Reiter Et Almentioning

confidence: 99%

Section: Cells and Retrovirusesmentioning

confidence: 99%

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WS5, a direct target of oncogenic transcription factor Myc, is related to human melanoma glycoprotein genes and has oncogenic potential

et al. 2006

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Siderocalins: siderophore-binding proteins of the innate immune system

2009

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Siderocalins: Siderophore binding proteins evolved for primary pathogen host defense

Sia

Allred

Raymond

2013

Current Opinion in Chemical Biology

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Bacterial pathogens use siderophores to obtain iron from the host in order to survive and grow. The host defends against siderophore-mediated iron acquisition by producing siderocalins. Siderocalins are a siderophore binding subset of the lipocalin family of proteins. The design of the siderophore binding pocket gives siderocalins the ability to bind a wide variety of siderophores and protect the host against several pathogens. Siderocalins have been identified in humans, chickens, and quail, among other animals. The differences in the respective siderocalins suggest that each was developed in response to the most serious pathogens encountered by that animal. Additionally, siderocalins have been observed in many roles unrelated to pathogen defense including differentiation, embryogenesis, inflammation, and cancer.

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Cell Transformation by the v-myc Oncogene Abrogates c-Myc/Max-mediated Suppression of a C/EBPβ-dependent Lipocalin Gene

Cited by 18 publications

References 79 publications

WS5, a direct target of oncogenic transcription factor Myc, is related to human melanoma glycoprotein genes and has oncogenic potential

WS5, a direct target of oncogenic transcription factor Myc, is related to human melanoma glycoprotein genes and has oncogenic potential

Siderocalins: siderophore-binding proteins of the innate immune system

Siderocalins: Siderophore binding proteins evolved for primary pathogen host defense

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