Expression of a 91-kilodalton PEA3-binding protein is down-regulated during differentiation of F9 embryonal carcinoma cells.

Martin, Mark; Yang, Xiu-Ying; Folk, William R.

doi:10.1128/mcb.12.5.2213

Cited by 31 publications

(22 citation statements)

References 61 publications

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“…2C, RL). A PEA3-like protein with a size of 91 kDa has also been described (30). The doublet at 60 and 58 kDa likely results from alternative splice events, with the 58-kDa isoform translated from an RNA splice variant lacking exon 7 and the 60-kDa isoform derived from an RNA lacking exon 2 (16a).…”

Section: Resultsmentioning

confidence: 99%

A Role for the ETS Domain Transcription Factor PEA3 in Myogenic Differentiation

Taylor

Dupont‐Versteegden

Davies

et al. 1997

Molecular and Cellular Biology

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Activation of adult myoblasts called satellite cells during muscle degeneration is an important aspect of muscle regeneration. Satellite cells are believed to be the only myogenic stem cells in adult skeletal muscle and the source of regenerating muscle fibers. Upon activation, satellite cells proliferate, migrate to the site of degeneration, and become competent to fuse and differentiate. We show here that the transcription factor polyomavirus enhancer activator 3 (PEA3) is expressed in adult myoblasts in vitro when they are proliferative and during the early stages of differentiation. Overexpression of PEA3 accelerates differentiation, whereas blocking of PEA3 function delays myoblast fusion. PEA3 activates gene expression following binding to the ets motif most efficiently in conjunction with the transcription factor myocyte enhancer factor 2 (MEF2). In vivo, PEA3 is expressed in satellite cells only after muscle degeneration. Taken together, these results suggest that PEA3 is an important regulator of activated satellite cell function.In mature muscle, activation of adult myoblasts called satellite cells is one mechanism for the maintenance of skeletal muscle mass. Although quiescent in normal muscle, these cells are activated to proliferate and differentiate in response to muscle damage or degeneration, thereby regenerating muscle fibers (5). To identify regulatory molecules in satellite cells that respond to external signals and control gene expression during satellite cell activation, we analyzed the regulation of the human ␤-enolase gene, which belongs to a relatively small group of muscle-specific genes expressed in proliferating, undifferentiated myoblasts from adult muscle (42). We showed that expression of the ␤-enolase gene in undifferentiated myoblasts is independent of the basic helix-loop-helix (bHLH) family of transcription factors, including MyoD, myogenin, myf-5, and MRF4 (42). Through comparative deletion-transfection analyses of myoblast and fibroblast cell lines, we identified an enhancer from the human ␤-enolase gene that promoted highlevel myoblast-specific expression of a reporter gene (49). After myoblast differentiation into myotubes, the activity of the enhancer declined dramatically, suggesting that other cis-regulatory elements are responsible for maintaining ␤-enolase gene expression in myotubes. Electrophoretic mobility shift assays and mutational analysis indicated that proteins present in myoblast nuclear extracts specifically bound to an ets motif within the enhancer required for high-level activity in myoblasts (49). ETS proteins comprise a family of transcription factors that share a conserved 85-amino-acid domain necessary for specific binding to purine-rich DNA sequences with a GGA core consensus (22, 38). They have been shown to be involved in regulating gene expression and controlling cell growth, differentiation, and migration in a variety of biological systems (21, 47, 52).A feature of many ETS domain proteins is that they form complexes with transcription factors of un...

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Section: Resultsmentioning

confidence: 99%

A Role for the ETS Domain Transcription Factor PEA3 in Myogenic Differentiation

Taylor

Dupont‐Versteegden

Davies

et al. 1997

Molecular and Cellular Biology

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“…The involvement of ETS-related transcription factors in preimplantation mouse development has been suggested in earlier studies that included EC cells, although endogenous targets for their activities had not been identified. Two ETS-related factors, PEA3 (62) and a distinct PEA3-like binding activity (36), are found in undifferentiated EC cells but are down regulated upon differentiation. The low levels of ETS-1 and AP-1 components and the induced levels of ETS-2 mRNAs that we observe in differentiating ES cell cultures (Fig.…”

Section: Discussionmentioning

confidence: 99%

AP-1, ETS, and transcriptional silencers regulate retinoic acid-dependent induction of keratin 18 in embryonic cells.

Pankov¹,

Neznanov²,

Umezawa³

et al. 1994

Mol. Cell. Biol.

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The differentiation of both embryonal carcinoma (EC) and embryonic stem (ES) cells can be triggered in culture by exposure to retinoic acid and results in the transcriptional induction of both the endogenous mouse keratin 18 (mK18) intermediate filament gene and an experimentally introduced human keratin 18 (K18) gene as well as a variety of other markers characteristic of extraembryonic endoderm. The induction of K18 in EC cells is limited, in part, by low levels of ETS and AP-1 transcription factor activities which bind to sites within a complex enhancer element located within the first intron of K18. RNA levels of ETS-2, c-Jun, and JunB increase upon the differentiation of ES cells and correlate with increased expression of K18. Occupancy of the ETS site, detected by in vivo footprinting methods, correlates with K18 induction in ES cells. In somatic cells, the ETS and AP-1 elements mediate induction by a variety of oncogenes associated with the ras signal transduction pathway. In EC cells, in addition to the induction by these limiting transcription factors, relief from negative regulation is mediated by three silencer elements located within the first intron of the K18 gene. These silencer elements function in F9 EC cells but not their differentiated derivatives, and their activity is correlated with proteins in F9 EC nuclei which bind to the silencers and are reduced in the nuclei of differentiated F9 cells. The induction of K18, associated with the differentiation of EC cells to extraembryonic endoderm, is due to a combination of relief from negative regulation and activation by members of the ETS and AP-1 transcription factor families.

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“…2B, C). On the other hand, neither the perfect SP1 recognition sequence (CCCCGCCC) [44], which is present at positions -148 to -141 bp of class 2 PSG genes (PSG6, PSG11) where it has been shown to have functional importance [45], nor the PEA3 consensus sequence (AGGAAG) [46] at position -60 to -54 bp relative to the initiation codon in the 5'-untranslated region of the PSGlZ gene, are found in ceal0 (Fig. 2B, C).…”

Section: Lp-2 -91 T~c T C T G C T M G M G a G C A G G G C A G A L A Cmentioning

confidence: 99%

The Cea10 Gene Encodes A Secreted Member of the Murine Carcinoembryonic Antigen Family and is Expressed in the Placenta, Gastrointestinal Tract and Bone Marrow

Keck

Nédellec

Beauchemin

et al. 1995

European Journal of Biochemistry

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Although members of the carcinoembryonic antigen (CEA) family have been shown to convey cell adhesion in vitro, their location in some tissues contradicts such a function. As a basis for investigating their in vivo functions, we are characterizing the mouse CEA family. This paper describes the structure and expression of a new murine family member, ceal0. Two full-length cDNA clones were isolated from a mouse colon library, whose deduced protein sequence comprises two immunoglobulin variable-like Ndomains, directly followed by a short C-terminal domain indicating that this molecule is secreted. Although this domain organization suggests a closer relationship to the murine pregnancy-specific glycoproteins (PSG), which form a subgroup within the CEA family, sequence comparisons place CealO within the CEA subgroup. Overlapping cosmid clones containing the complete ceal0 locus were mapped and the exons determined. No AZ-like exon, characteristic for all other members of the murine CEA family, could be found. Sequences of the promoter and the first exon showed remarkably high similarity to the corresponding regions of bgpl and bgp2, two other members of the murine CEA subgroup. Consensus sequences for two transcription factors (USF and an AP-2-like factor) that bind to the human BGP gene promoter were also present in the cealO promoter and possibly convey expression of these genes in epithelial cells. RNase protection assays revealed transcriptional activity of cealO in the colon and early placenta (10.5-12.5-day embryos) and to a lower extent in the small intestine, cecum, stomach, salivary glands and bone marrow. As some other CEA family members are deregulated in tumors, we quantified the expression levels of CealO transcripts in colonic mucosa and in adenomatous polyps of M i d + mice. No differences in the steady-state levels of CealO mRNA could be found, suggesting that the CealO protein does not play a role in early tumor development. Taken together, CealO combines characteristic features of both CEA and PSG subgroup members in its structure and expression pattern.

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Expression of a 91-kilodalton PEA3-binding protein is down-regulated during differentiation of F9 embryonal carcinoma cells.

Cited by 31 publications

References 61 publications

A Role for the ETS Domain Transcription Factor PEA3 in Myogenic Differentiation

A Role for the ETS Domain Transcription Factor PEA3 in Myogenic Differentiation

AP-1, ETS, and transcriptional silencers regulate retinoic acid-dependent induction of keratin 18 in embryonic cells.

The Cea10 Gene Encodes A Secreted Member of the Murine Carcinoembryonic Antigen Family and is Expressed in the Placenta, Gastrointestinal Tract and Bone Marrow

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