Metastasis-associated protein 1 (MTA1) is an essential downstream effector of the c-MYC oncoprotein

Zhang, Xiao Yong; DeSalle, Lauren M; Patel, Jagruti; Capobianco, Anthony J.; Yu, Duonan; Thomas-Tikhonenko, Andrei; McMahon, Steven B.

doi:10.1073/pnas.0502330102

Cited by 111 publications

(116 citation statements)

References 46 publications

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“…62 In the current studies, MTA1 transcription was up-regulated by TGFb1 in a time frame consistent with c-Myc activation. We postulate that this metastasis factor, recently shown to be overexpressed in malignant primary GI carcinoids and their metastases 27,63 and linked to a worse prognosis in EC cellderived appendiceal tumors, 28 is up-regulated by TGFb1 or the TGFb1-pathway in neoplastic EC cells and plays a role in malignant transformation and metastasis.…”

Section: Discussionmentioning

confidence: 57%

Small bowel carcinoid (enterochromaffin cell) neoplasia exhibits transforming growth factor–β1‐mediated regulatory abnormalities including up‐regulation of C‐Myc and MTA1

Kidd

Modlin

Pfragner

et al. 2007

Cancer

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Objective To examine whether and to what extent the intracellular trafficking features of HLA–B*2705, which is associated with the development of spondylarthritis (SpA), differ from those of HLA–B*2709 and HLA–B*0702, which are not associated with SpA. Methods HeLa cells were transfected with complementary DNA encoding for HLA–B proteins fused to Renilla luciferase or yellow fluorescent protein. The subcellular distribution of properly folded and unfolded/misfolded HLA–B proteins was examined by flow cytometry and confocal microscopy of cells labeled with ME1 and HC‐10 antibodies, respectively. HLA–B/HLA–B interactions were monitored in endoplasmic reticulum (ER)– and plasma membrane–enriched subcellular fractions, by bioluminescence resonance energy transfer (BRET). Results All 3 HLA–B alleles displayed a similar distribution pattern (properly folded heavy chain at the cell surface, unfolded/misfolded proteins only in the cytoplasm). By means of BRET, we provided evidence that both HLA–B*2705 and HLA–B*2709 formed more oligomers in the ER and the plasma membrane than did HLA–B*0702. The propensity of HLA–B*2705 to form oligomers in the ER was partly attributable to residue Cys67 of the molecule. For all 3 alleles, increased expression of HLA–B proteins was associated with intracytoplasmic accumulation of unfolded/misfolded proteins and intracellular vesicles, probably corresponding to expanded ER–Golgi intermediate compartments, in which these proteins accumulated together with the stress sensor BiP. Conclusion Our results suggest that the difference in disease susceptibility conferred by HLA–B*2705 and HLA–B*2709 cannot be explained by their different propensity to form dimers or misfolded proteins, thus presumably implicating other, still unknown factors.

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Section: Discussionmentioning

confidence: 57%

Small bowel carcinoid (enterochromaffin cell) neoplasia exhibits transforming growth factor–β1‐mediated regulatory abnormalities including up‐regulation of C‐Myc and MTA1

Kidd

Modlin

Pfragner

et al. 2007

Cancer

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“…Using the chromatin immunoprecipitation (ChIP) assay, the rODC and rat metastasis-associated protein 1 (rMTA1) promoter regions were analysed (Zhang et al, 2005). rMTA1 and rODC promoters possess 10 and four E-boxes, respectively (Figure 6a).…”

Section: Resultsmentioning

confidence: 99%

“…Two downstream genes, MTA1 and ODC, are well documented to cause the c-Myc-mediated malignant phenotypes, including anchorage-independent growth (Nilsson et al, 2005;Zhang et al, 2005). Downregulation of rSGF29 in K2 cells, in which both rSGF29 and c-myc gene expressions were deregulated, caused the reduction of their colony-forming ability in soft agar, showing that deregulated expression of rSGF29 is implicated in malignant transformation.…”

Section: Discussionmentioning

confidence: 99%

Deregulated expression of a novel component of TFTC/STAGA histone acetyltransferase complexes, rat SGF29, in hepatocellular carcinoma: possible implication for the oncogenic potential of c-Myc

et al. 2007

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“…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). However, none of these genes can fully substitute for myc function.…”

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

confidence: 99%

“…Also, an important unresolved question is whether deregulated oncogenic Myc promotes tumorigenesis by aberrant regulation of its normal targets or by affecting new ones. Several Myc targets have recently been identified that display partial oncogenic potential (Ben-Porath et al, 1999;Zhang et al, 2005;O'Donnell et al, 2006). Notably, no target gene has been identified so far that can mimic the full oncogenic capacity of myc upon ectopic expression, supporting the notion that the molecular events downstream of myc represent a multifunctional response.…”

Section: Introductionmentioning

confidence: 97%

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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Metastasis-associated protein 1 (MTA1) is an essential downstream effector of the c-MYC oncoprotein

Cited by 111 publications

References 46 publications

Small bowel carcinoid (enterochromaffin cell) neoplasia exhibits transforming growth factor–β1‐mediated regulatory abnormalities including up‐regulation of C‐Myc and MTA1

Small bowel carcinoid (enterochromaffin cell) neoplasia exhibits transforming growth factor–β1‐mediated regulatory abnormalities including up‐regulation of C‐Myc and MTA1

Deregulated expression of a novel component of TFTC/STAGA histone acetyltransferase complexes, rat SGF29, in hepatocellular carcinoma: possible implication for the oncogenic potential of c-Myc

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

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