Transcriptional Activation of the Type II Transforming Growth Factor-β Receptor Gene upon Differentiation of Embryonal Carcinoma Cells

Kelly, David L.; Kim, Seong‐Jin; Rizzino, Angie

doi:10.1074/jbc.273.33.21115

Cited by 38 publications

(59 citation statements)

References 69 publications

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“…Moreover, the presence of the cancer marker hnRNP F [25] and hnRNP A/B [40] decreased in differentiated Bc holoenzymes as compared to Nd holoenzymes. This is consistent with the fact that differentiated P19 cells are non-tumorigenic as opposed to non-differentiated P19 cells [41], and suggests that holoenzymes from cycling or tumorigenic cells may be lacking regulatory subunits.…”

Section: Discussionsupporting

confidence: 72%

Proteomics of RNA polymerase II holoenzymes during P19 cardiomyogenesis

Maës

2007

Open Life Sciences

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Abstract:The embryonal carcinoma P19 model has allowed the elucidation of a role for several transcription factors in cell differentiation. Here, the regulation of the RNA polymerase II machinery has been explored through its association with multifunctional complexes involved in transcription. An interaction proteomics analysis of TFIIS-purified RNA polymerase II (RNAPII) holoenzymes during cardiomyogenesis is described. Modifications of protein complexes that may be associated with transcriptionally active and activator responsive RNAPII holoenzymes were detected in a serum and DMSO dependent manner. Subunits of the PAF1 and Mediator complexes were correlated with holoenzymes from non-differentiated and terminally differentiated P19 cultures respectively. Moreover, high levels of nucleolin were identified in all forms of holoenzymes by two-dimensional gel electrophoresis, and suggest that nucleolin could bind to RNAPII and TFIIS. Several proteins that were identified in the RNAPII holoenzymes are known to have functions in mRNA processing and may bind to nucleolin. A novel function for nucleolin is proposed as a possible pivotal platform between transcription, mRNA processing and export.

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Section: Discussionsupporting

confidence: 72%

Proteomics of RNA polymerase II holoenzymes during P19 cardiomyogenesis

Maës

2007

Open Life Sciences

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“…Hence, reporter activity in the differentiated cells is unlikely to be due to residual undifferentiated EC cells. Currently, the reason for this common observation is unclear, but similar observations have been made for the FGF-4, TβR-II, and TGF-β2 genes (Ma et al, 1992;Kelly et al, 1995Kelly et al, , 1998, which are differentially expressed by F9 EC cells and their differentiated counterparts. Figure 5.…”

Section: Effect Of Differentiation On the Sox-2 Promoter Constructsmentioning

confidence: 77%

“…Interestingly, the FGF-4, TβR-II, and CYP1A1 genes each contain identical CCAAT box-like sequence motifs in each of their respective promoters (5′-TGATTGGCAG-3′). Unlike the Sox-2 CCAAT box motif, gel mobility shift analysis of the FGF-4, TβR-II, and CYP1A1 CCAAT box motifs revealed formation of two distinct DNA/protein complexes, one of which contains NF-Y (Boucher et al, 1993(Boucher et al, , 1995Lamb et al, 1997;Kelly et al, 1998). Both complexes are specific for the CCAAT box-like motif, as an unlabeled FGF-4, TβR-II, or CYP1A1 mutant CCAAT box competitor, in which only the CCAAT box has been scrambled, does not compete for either complex (Kelly and Rizzino, unpublished data).…”

Section: Discussionmentioning

confidence: 99%

“…These genes all contain the sequence (5′-TGATTGGC AG-3′), which differs by only one base pair (underlined) with the Sox-2 CCAAT box (5′-TGATTGGCCG-3′). Previous gel mobility shift assays demonstrated that the CCAAT box motif from each of these three genes can form two DNA/protein complexes, one of which contains NF-Y (Boucher et al, 1993(Boucher et al, , 1995Lamb et al, 1997;Kelly et al, 1998). To determine whether NF-Y binds the Sox-2 CCAAT box motif, we performed gel mobility shift analysis using a dsODN probe containing the CCAAT box sequence of the Sox-2 promoter.…”

Section: Role Of a Consensus Ccaat Box Motif Present In The Sox-2 Promentioning

confidence: 99%

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Isolation, characterization, and differential expression of the murine Sox-2 promoter

Wiebe

Wilder

Kelly

et al. 2000

Gene

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Sox proteins are expressed at many stages of development and in numerous tissues. The transcription factor Sox-2 is first expressed throughout the inner cell mass and subsequently becomes localized to the primitive ectoderm, developing central nervous system, and the lens. Sox-2 is also highly expressed in F9 embryonal carcinoma cells but becomes undetectable following differentiation of these cells. In this study, we have isolated, sequenced, and performed the first characterization of the Sox-2 promoter of any species. Approximately 2 kb of the Sox-2 5′-flanking region has been sequenced and the primary transcription start site mapped by primer extension analysis. Additionally, two positive regulatory regions within the promoter region have been identified. We also show that expression of Sox-2 promoter/reporter gene constructs is reduced in differentiated EC cells as compared to their undifferentiated counterparts. Furthermore, we have identified a consensus inverted CCAAT box motif present in the Sox-2 promoter. Mutagenesis of this site significantly reduces the expression of Sox-2 promoter/reporter constructs. We also demonstrate that this CCAAT box motif can bind the trimeric transcription factor NF-Y.

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“…This region has been shown to contain an AP1/CRE site (22), which is an important determinant during the differentiation of EC cells (27). Of related interest is the fact that some breast cancer cells have been shown to be deficient in the activity of AP1 (28).…”

Section: Fig 4 Sp1-dependent Promoter (Igf-ii Promoter) Activity Inmentioning

confidence: 99%

The Role of Sp1 in the Differential Expression of Transforming Growth Factor-β Receptor Type II in Human Breast Adenocarcinoma MCF-7 Cells

Liu¹,

Zhong²,

Li³

et al. 2000

Journal of Biological Chemistry

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Progression of MCF-7 cells from early passage (MCF-7E, <200 passage) to late passage (MCF-7L, >500 passage) correlates with a loss of sensitivity to exogenous TGF␤1. We have previously shown that loss of TGF␤ sensitivity is due to decreased expression of the transforming growth factor receptor type II (T␤RII) and is associated with increased tumorigenicity in nude mice. Reduced T␤RII expression in MCF-7L cells is caused by decreased T␤RII promoter activity in this cell line. Our previous studies using 5 deletion constructs of this promoter revealed that MCF-7L cells were unable to support transcription of the minimal promoter (؊47 to ؉2) to the same levels as the MCF-7E cells. This region of the promoter contains an Sp1 element at position ؊25 from the major transcription start site. In this study, we in- T␤RIII is thought to play a role in presenting the ligand to the other receptors (6). Receptor type I (T␤RI), a 50 -60-kDa glycoprotein, and receptor type II (T␤RII), a 75-85-kDa glycoprotein, belong to a superfamily of receptor serine/threonine kinases. The presence of both T␤RI and T␤RII is necessary to effect a TGF␤ response, and both kinase activities must be functional for proper signal transduction (7-10). Therefore, cells defective in one or the other receptor are refractory to the effects of TGF␤ and escape its autocrine-negative effects on growth.The loss of TGF␤ sensitivity has been correlated to tumor progression. This loss has been most often associated with a loss of T␤RII expression (11). Replication error-positive colorectal cancer cells show a mutation in T␤RII coding region, which results in message instability and loss of protein (12)(13)(14). Deletion of the T␤RII gene, loss of T␤RII message, and expression of a truncated T␤RII message have also been observed in other cancer cell lines (15)(16)(17)(18)(19)(20).The human breast cancer MCF-7 cells have no detectable cell surface T␤RII and are refractory to the effects of TGF␤ (18,19). The re-expression of T␤RII in these cells restores their sensitivity to the growth inhibitory effects of TGF␤ (19). In addition, the transfectants showed decreased anchorage-independent growth, and a decreased tumorigenicity in nude mice compared with vector-transfected cells. These results suggest that T␤RII behaves as a tumor suppressor in the MCF-7 cells.Due to the significant role of T␤RII in determining tumorigenicity, it is likely that defects of T␤RII expression can lead to malignant progression. MCF-7 cells represent a well established model system for studying the biology of breast cancer cells. Our earlier work using MCF-7 early passage (MCF-7E) and MCF-7 late passage (MCF-7L) cells demonstrated that MCF-7L cells' resistance to exogenous TGF␤ correlated with the low, or undetectable level of T␤RII in this cell line (18).

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Transcriptional Activation of the Type II Transforming Growth Factor-β Receptor Gene upon Differentiation of Embryonal Carcinoma Cells

Cited by 38 publications

References 69 publications

Proteomics of RNA polymerase II holoenzymes during P19 cardiomyogenesis

Proteomics of RNA polymerase II holoenzymes during P19 cardiomyogenesis

Isolation, characterization, and differential expression of the murine Sox-2 promoter

The Role of Sp1 in the Differential Expression of Transforming Growth Factor-β Receptor Type II in Human Breast Adenocarcinoma MCF-7 Cells

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