The product of a fos-related gene, fra-1, binds cooperatively to the AP-1 site with Jun: transcription factor AP-1 is comprised of multiple protein complexes.

Cohen, Donna R.; Ferreira, P. C. P.; Gentz, Reiner; Franza, B. R.; Curran, Tom

doi:10.1101/gad.3.2.173

Cited by 301 publications

(145 citation statements)

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“…The DNA-binding speci®city of Fra-1/Jun heterodimers was found to be indistinguishable from that of c-Fos/Jun heterodimers using several AP-1 sites (Cohen et al, 1989). Fra-1 exhibits oncogenic potential similar to, but weaker than that of c-Fos, since overexpression in established rat ®broblasts leads to anchorage-independent growth and tumor development in athymic mice (Bergers et al, 1995).…”

Section: Introductionmentioning

confidence: 95%

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Structure and chromosomal assignment of the mouse fra-1 gene, and its exclusion as a candidate gene for oc (osteosclerosis)

et al. 1997

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We have determined the genomic structure of the mouse fra-1 gene, which consists of four exons and three introns at positions also found in the other members of the fos gene family. Fra-1 is expressed rather highly in the brain and testes of adult mice, and at low levels in most other tissues. Absence of c-Fos leads to signi®cantly reduced serum stimulation of fra-1 expression in gene targeted mouse ®broblasts, demonstrating that mitogen induction of fra-1 is partially mediated by c-Fos/AP-1. A polymorphic (CA) n microsatellite marker was found in intron 2 of fra-1 and used to map the gene to the centromeric region of mouse chromosome 19. Since fra-1 maps to the same genomic region as oc (osteosclerosis), an autosomal recessive disorder leading to the bone remodelling disease osteopetrosis, we tested it as a candidate gene for oc. The segregation of fra-1 in two di erent crosses of mice carrying oc and an allelism test between oc and a targeted disruption of fra-1 demonstrate that fra-1 and oc are two distinct genes rather than oc being a mutant allele of fra-1.

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Section: Introductionmentioning

confidence: 95%

“…The cellular immediate early gene fra-1 (Fos-related antigen 1) encodes an AP-1 subunit which belongs to the Fos-subfamily (Cohen and Curran, 1988;Cohen et al, 1989). The DNA-binding speci®city of Fra-1/Jun heterodimers was found to be indistinguishable from that of c-Fos/Jun heterodimers using several AP-1 sites (Cohen et al, 1989).…”

Section: Introductionmentioning

confidence: 99%

Structure and chromosomal assignment of the mouse fra-1 gene, and its exclusion as a candidate gene for oc (osteosclerosis)

et al. 1997

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“…In neoplastic conditions, including a subset of human colorectal cancers, cyclin D1 overexpression has been observed. [23][24][25] Fra-1 is a member of the fos protooncogene family 26,27 and its role in the development of epithelial tumors has recently been suggested. 28,29 There has been no study to date, however, of Fra-1 expression in human colorectal neoplasms.…”

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confidence: 99%

Elevated protein expression of cyclin D1 and Fra‐1 but decreased expression of c‐Myc in human colorectal adenocarcinomas overexpressing β‐catenin

Wang

Xiao

et al. 2002

Intl Journal of Cancer

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Mutations of the adenomatous polyposis coli tumor suppressor gene, or its downstream target ␤-catenin, have been implicated in the initiation of most sporadic human colorectal epithelial neoplasms. These mutations, in turn, lead to aberrant nuclear accumulation of ␤-catenin and subsequent activation of the ␤-catenin/Tcf transcription factor complex. In vitro studies utilizing cultured human colon cancer cell lines have identified c-myc, cyclin D1 and fra-1 as target genes of ␤-catenin/Tcf signaling. In our study, 12 cases of human colorectal adenocarcinomas were examined by Western immunoblotting analysis and immunohistochemical staining to specifically investigate whether the protein expression of these target genes was indeed altered in vivo by ␤-catenin dysregulation. The results show that the protein level of ␤-catenin was significantly increased in all 12 tumors (3.4 ؎ 1.0-fold increase compared to the control normal mucosa by Western immunoblotting, p < 0.05), and this increase was associated with positive nuclear staining by immunohistochemistry in 10 cases. Increased levels of expression of cyclin D1 and Fra-1 proteins were also demonstrated in every tumor (9.0 ؎ 2.7 and 3.3 ؎ 0.9-fold increases compared to normal mucosa, respectively). Surprisingly, the protein level of c-Myc was significantly decreased in all tumors examined by 49 ؎ 19% (p < 0.05), but the c-myc mRNA level was increased in 8 of 12 tumors when compared to that in normal mucosa by RT-PCR. Immunohistochemical staining performed on these carcinomas and additional 27 colorectal carcinomas further demonstrated that the protein expression level of c-Myc and ␤-catenin nuclear localization were not correlated. Moreover, 15 of 20 colorectal adenomas exhibited positive nuclear ␤-catenin immunostaining, among which 11 also exhibited increased c-Myc protein expression. These data thus support the notion that upregulation of cyclin D1 and Fra-1 in human colorectal adenocarcinomas is driven by abnormally expressed ␤-catenin. However, the regulation of c-myc expression in colorectal tumors appears to be more complex. While dysregulated ␤-catenin may cause a transcriptional upregulation of the c-myc gene, the c-Myc protein expression appears to be further regulated by a posttranscriptional mechanism(s) during the process of neoplastic progression.

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“…The three Jun proteins, c-Jun, JunB, and JunD, can form homodimers and bind to an AP-1 site, but they differ in their binding affinities (33), and it has been demonstrated, at least for c-Jun and JunB, that they have different transcriptional and biological activities (4,36,37). The Fos proteins, c-Fos, FosB, Fra-1, and Fra-2, differ from the Jun proteins in that they do not form homodimers and have no intrinsic specific DNA binding activity (6,9,24,39,42). However, the binding affinity and transcriptional activation of the Jun proteins are dramatically increased upon dimerization with Fos proteins (6,9,23,28,29,33,39,42).…”

mentioning

confidence: 99%

Existence of different Fos/Jun complexes during the G0-to-G1 transition and during exponential growth in mouse fibroblasts: differential role of Fos proteins.

Kovary¹,

Bravo²

1992

Mol. Cell. Biol.

200

111

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We have determined the different Fos/Jun complexes present in Swiss 3T3 cells either following serum stimulation of quiescent cells or during exponential growth by immunoprecipitation analyses. We have shown that while c-Fos is the major Fos protein associated with the Jun proteins (c-Jun, JunB, and JunD) soon after serum stimulation, at later times Fra-1 and Fra-2 are the predominant Fos proteins associated with the different Jun proteins. During exponential growth, the synthesis of Fra-1 and Fra-2 is maintained at a significant level, in contrast to c-Fos and FosB, which are expressed at very low or undetectable levels. Consequently, Fra-1 and Fra-2 are the main Fos proteins complexed with the Jun proteins in asynchronously growing cells. To determine whether the Fos proteins are differentially required during the G0-to-G1 transition and exponential growth for the entrance into S phase, we microinjected affinity-purified antibodies directed against c-Fos, FosB, Fra-1, and Fra-2. We have found that while the activities of c-Fos and FosB are required mostly during the G0-to-G1 transition, Fra-1 and Fra-2 are involved both in the G0-to-G1 transition and in asynchronous growth.

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The product of a fos-related gene, fra-1, binds cooperatively to the AP-1 site with Jun: transcription factor AP-1 is comprised of multiple protein complexes.

Cited by 301 publications

References 39 publications

Structure and chromosomal assignment of the mouse fra-1 gene, and its exclusion as a candidate gene for oc (osteosclerosis)

Structure and chromosomal assignment of the mouse fra-1 gene, and its exclusion as a candidate gene for oc (osteosclerosis)

Elevated protein expression of cyclin D1 and Fra‐1 but decreased expression of c‐Myc in human colorectal adenocarcinomas overexpressing β‐catenin

Existence of different Fos/Jun complexes during the G0-to-G1 transition and during exponential growth in mouse fibroblasts: differential role of Fos proteins.

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