Analysis of genomic targets reveals complex functions of MYC

Patel, Jagruti; Loboda, Andrey; Showe, Michael K.; Showe, Louise C.; McMahon, Steven B.

doi:10.1038/nrc1393

Cited by 271 publications

(248 citation statements)

References 68 publications

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“…WS5, a direct transcriptional target of Myc F Reiter et al be identified and analysed. This is a considerable challenge since key transcriptional regulators like Myc, involved in the control of many fundamental biological processes, affect the expression of many genes (Neiman et al, 2001;Menssen and Hermeking, 2002;Patel et al, 2004). However, not all of these genes are necessarily effectors of the biological functions of Myc (Grandori et al, 2000;Eisenman, 2001).…”

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

confidence: 99%

“…For validation of a direct target, binding of Myc in vivo and tight correlation of transcriptional alterations with Myc expression is required (Eisenman, 2001). Several direct Myc targets have been well defined (Dang, 1999;Grandori et al, 2000;Hermeking et al, 2000;Eisenman, 2001;Patel et al, 2004), most of them with biological functions in cell cycle control, metabolism or ribosome biogenesis, but only a few have so far been directly linked to the transforming function of Myc (Eisenman, 2001, Patel et al, 2004. These include the ornithine decarboxylase gene (ODC), the tumor-associated membrane glycoprotein gene Tmp, the metastasis-associated protein 1 (MTA1) gene, or the transferrin receptor 1 (TFRC1) gene, that were shown to have oncogenic potential (BenPorath et al, 1999;Eisenman, 2001;Zhang et al, 2005;O'Donnell et al, 2006).…”

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

confidence: 99%

“…Myc is involved in many basic cellular functions, and recent studies have suggested that it may regulate, directly or indirectly, up to 15% of all genes (Patel et al, 2004). For target gene validation, distinction between direct and indirect effects on gene expression is essential.…”

Section: Introductionmentioning

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 Almentioning

confidence: 99%

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

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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“…Myc is isolated from nuclei in heterodimers with Max and binds to DNA at CACGTG and related sequences. Comprehensive analysis of Mycregulated transcription reveals that in a whole range of cell lineages, Myc activates and represses an approximately equivalent number of genes (Patel et al, 2004;. When Myc binds to its consensus sites, it recruits cofactors such as TRRAP and Skp2, which mediate transactivation .…”

Section: Introductionmentioning

confidence: 99%

An N-Myc truncation analogous to c-Myc-S induces cell proliferation independently of transactivation but dependent on Myc homology box II

Cowling

Cole

2007

Oncogene

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“…It has been reported that enolase-α also plays an important role in the regulation of c-myc promoter activity in the form of alternative translation product MBP-1 (37-40 kDa), which is distinct from its role as a glycolytic enzyme [59][60][61][62]. The c-myc proto-oncogene is known as an essential part of normal cell proliferative machinery [63,64]. MPB-1, structurally very similar to enolase-α, binds to the c-myc P2 promoter and down-regulates c-myc expression, and therefore, suppresses cell proliferation [60][61][62].…”

Section: Cooperation Of Npm and Enolase-α In Pbrmentioning

confidence: 99%

Proteome analysis of proliferative response of bystander cells adjacent to cells exposed to ionizing radiation

Gerashchenko

Yamagata²,

Oofusa³

et al. 2007

Proteomics

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Recently (Cytometry 2003, 56A, 71-80), we reported that direct cell-to-cell contact is required for stimulating proliferation of bystander rat liver cells (WB-F344) cocultured with irradiated cells, and neither functional gap junction intercellular communication nor long-range extracellular factors appear to be involved in this proliferative bystander response (PBR). The molecular basis for this response is unknown. Confluent monolayers of WB-F344 cells were exposed to 5-Gray (Gy) of γ-rays. Irradiated cells were mixed with unirradiated cells and co-cultured for 24 h. Cells were harvested and protein expression was examined using 2-DE. Protein expression was also determined in cultures of unirradiated and 5-Gy irradiated cells. Proteins were identified by MS. Nucleophosmin (NPM)-1, a multifunctional nucleolar protein, was more highly expressed in bystander cells than in either unirradiated or 5-Gy irradiated cells. Enolase-α, a glycolytic enzyme, was present in acidic and basic variants in unirradiated cells. In bystander and 5-Gy irradiated cells, the basic variant was weakly expressed, whereas the acidic variant was overwhelmingly present. These data indicate that the presence of irradiated cells can affect NPM-1 and enolase-α in adjacent bystander cells. These proteins appear to participate in molecular events related to the PBR and suggest that this response may involve cellular defense, proliferation, and metabolism.

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Analysis of genomic targets reveals complex functions of MYC

Cited by 271 publications

References 68 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

An N-Myc truncation analogous to c-Myc-S induces cell proliferation independently of transactivation but dependent on Myc homology box II

Proteome analysis of proliferative response of bystander cells adjacent to cells exposed to ionizing radiation

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