Transcriptional regulation and transformation by Myc proteins

Adhikary, Sovana; Eilers, Martin

doi:10.1038/nrm1703

Cited by 1,015 publications

(964 citation statements)

References 150 publications

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“…We chose to focus on c-MYC that is overexpressed in various human tumors (Adhikary and Eilers, 2005). We also used BMSCs isolated from the Ink4aKO mice in addition to those from wild-type (WT) mice, because recent reports suggest a close correlation between Ink4a inactivation and the maintenance of the tissue stem cell population (Janzen et al, 2006;Molofsky et al, 2006;Shibata et al, 2007).…”

Section: Establishment Of Ink4akomentioning

confidence: 99%

c-MYC overexpression with loss of Ink4a/Arf transforms bone marrow stromal cells into osteosarcoma accompanied by loss of adipogenesis

et al. 2010

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The development of cancer is due to the growth and proliferation of transformed normal cells. Recent evidence suggests that the nature of oncogenic stress and the state of the cell of origin critically affect both tumorigenic activity and tumor histological type. However, this mechanistic relationship in mesenchymal tumors is currently largely unexplored. To clarify these issues, we established a mouse osteosarcoma (OS) model through overexpression of c-MYC in bone marrow stromal cells (BMSCs) derived from Ink4a/Arf (À/À) mice. Single-cell cloning revealed that c-MYC-expressing BMSCs are composed of two distinctly different clones: highly tumorigenic cells, similar to bipotent-committed osteochondral progenitor cells, and low-tumorigenic tripotent cells, similar to mesenchymal stem cells (MSCs). It is noteworthy that both bipotent and tripotent cells were capable of generating histologically similar, lethal OS, suggesting that both committed progenitor cells and MSCs can become OS cells of origin. Shifting mesenchymal differentiation by depleting PPARc in tripotent MSC-like cells and overexpressing PPARc in bipotent cells affected cell proliferation and tumorigenic activity. Our findings indicate that differentiation potential has a key role in OS tumorigenic activity, and that the suppression of adipogenic ability is a critical factor for the development of OS.

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Section: Establishment Of Ink4akomentioning

confidence: 99%

c-MYC overexpression with loss of Ink4a/Arf transforms bone marrow stromal cells into osteosarcoma accompanied by loss of adipogenesis

et al. 2010

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“…A subset of Myc-repressed genes require Miz-1, a protein that binds to the Myc DNA-binding domain (Adhikary and Eilers, 2005). We utilized a c-Myc mutant, c-MycV394D, which does not bind to Miz-1 to determine if Myc promoter repression and GADD45a repression requires Miz-1 (Herold et al, 2002).…”

Section: C-myc-s-induced Proliferation Is Mbii-dependent Vh Cowling Amentioning

confidence: 99%

“…In addition, Myc-dependent repression is largely dependent on Myc Box II domain, a conserved region in the transactivation domain through which most cofactors bind . Several different models of Myc-dependent repression have been reported, most involving Myc/Max recruitment to promoters via binding to another DNA-binding protein such as p300, Miz-1 or YY1 (Adhikary and Eilers, 2005). In this model, it remains unclear why repression is dependent on a functional Myc DNA-binding domain.…”

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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“…The dimeric Myc-Max and Max-Mad transcription factors recruit co-activator or corepressor complexes that modify chromatin structure and modulate transcription. They are key regulators of genes critically involved in cellular growth, proliferation, metabolism, differentiation and apoptosis (Dang, 1999;Grandori et al, 2000;Eisenman, 2001;Secombe et al, 2004;Adhikary and Eilers, 2005).…”

Section: Introductionmentioning

confidence: 99%

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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Transcriptional regulation and transformation by Myc proteins

Cited by 1,015 publications

References 150 publications

c-MYC overexpression with loss of Ink4a/Arf transforms bone marrow stromal cells into osteosarcoma accompanied by loss of adipogenesis

c-MYC overexpression with loss of Ink4a/Arf transforms bone marrow stromal cells into osteosarcoma accompanied by loss of adipogenesis

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

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

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