Disease relevance of FOSL2

• It was therefore of interest to determine the cytogenetic localization of the human Fra-2 gene (FRA2), including a comparison to chromosomal aberrations observed in leukemia patients [1].
• We demonstrate that the CBP/p300 coactivator is recruited by the HPV18 enhanceosome and that it is limiting for transcriptional activation, since it is sequestered by the adenovirus E1A protein and by the JunB/Fra2 positive factor in excess [2].
• In the present study, the expression of members of the AP-1 family of transcription factors in breast tumors (n = 53) was investigated by Western blot with antibodies specific for each of the AP-1 family members (c-jun, junB, junD and c-fos, fosB, fra1 and fra2) [3].
• In choriocarcinomas, there was a strong expression for c-Jun, JunD, Fra1, and Fra2 [4].

High impact information on FOSL2

• The nontransforming proteins Fra1 and Fra2 can be converted to transforming proteins by fusion of a transactivation domain from either FosB or VP16 [5].
• In contrast, PTX-B inhibited AP-1 binding to target DNA and modified its composition with a proportional increases in FosB, Fra2, and ATF2 [6].
• Utrophin enhancer activity was dependent on an AP-1 site, and in satellite cells of regenerating muscle the AP-1 factors Fra1, Fra2, and JunD were strongly induced [7].
• In untreated cells, SPRR1B promoter is predominantly occupied by JunD and Fra2 [8].
• Avian primary cells transformed by either Jun : Fra2 or Jun : ATF2 thus provide powerful tools for the investigation of the downstream pathways involved in oncogenesis [9].

Biological context of FOSL2

• The localization of the gene to chromosome 2 was independently verified by PCR amplification of a FRA2-specific fragment from a panel of rodent-human somatic cell hybrids [1].
• When studying cAMP-induced apoptosis in a leukemia cell line from rat, we found that the Fra-2 gene (coding for the Fos-related antigen-2) became strongly upregulated as the leukemia cells started to die [1].
• This fragment was employed as probe for both radioactive and fluorescence in situ hybridization to human metaphase chromosomes, allowing us to assign FRA2 to 2p22-p23 [1].
• With the aim to identify the oncoprotein partners implicated in the c-Jun myogenic influence, we carried out stable transfection experiments of c-Jun and/or ATF2, Fra2, c-Fos overexpression in avian myoblasts [10].
• Whereas c-Fos and Fra2 cooperated with c-Jun to abrogate myoblast withdrawal from the cell cycle and terminal differentiation, ATF2 co-expression potentiated the positive myogenic c-Jun influence [10].

Anatomical context of FOSL2

• Intriguingly, overexpression of fra2 suppressed PMA-inducible reporter activity, whereas fra1 significantly enhanced basal level activity, indicating an opposing role for these proteins in SPRR1B expression in a manner similar to that observed in proximal tracheobronchial epithelial cells (BEAS-2B clone S6) [11].
• Four proteins (FBR-v-Fos, FBJ-v-Fos, c-Fos, and FosB) transform established rodent fibroblast cell lines, while three (FosB2, Fra1, and Fra2) do not [5].
• Interestingly, most AP-1 factors were expressed in the intermediate (extravillous) trophoblast, with expression being strongest for JunD and Fra2 (100% of nuclei showing strong expression), followed by c-Jun (80% positive nuclei), c-Fos and FosB (50% positive nuclei) [12].
• High levels of fra-2 mRNA were detected in ovary, stomach, small and large intestine, brain, lung and heart [13].
• RESULTS: Transcriptionally active AP-1 in combinations of c-Jun, JunD and JunB with Fra1, Fra2 and possibly FosB, are expressed in cardiac myocytes [14].

Associations of FOSL2 with chemical compounds

• FRA-2 protein represented the main component of the chronic amphetamine- or cocaine-activated complexes, which suggests its relevance in the long-term effects of psychostimulant drugs [15].
• Proteasomal inhibition, which reduced the NE-stimulated induction of aa-nat, caused a reduction of ICER and Fra-2 [16].
• Our laboratory has discovered that Fos-related antigen-2 from AP-1 transcription factor family and NF-kappa B p65 and p50 subunits are induced long-term (days to months) in the brain after neurotoxic, excitotoxic or ischemic insult [17].

Other interactions of FOSL2

• PMA significantly induced binding of JunB and Fra1 in normal cells, while JunB and Fra2 bound to TREs in the malignant cells [8].
• RESULTS: Of the seven AP-1 factors, three (c-fos, fra2, and junB) clearly showed higher expression levels in tumors when compared to matched normal endometrial samples [18].
• This TRE bound TPA induced specific nuclear complexes in vitro containing junD, c-jun, c-fos, and fra2 but not cAMP-responsive element binding/activating transcription factor family proteins [19].

Analytical, diagnostic and therapeutic context of FOSL2

• Of the 352 differentially expressed genes found, CD70 and FRA2 were selected for further evaluation by real-time RT-PCR [20].

References