Fosl1 14283

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Gene ID: 14283
Gene symbol: fosl1
Gene Description: fos-like antigen 1
Aliases: AW538199; fra-1; Fra1
Human Ortholog Gene ID: [8061]
Reviewer Judgement: TF Gene
Functional Classification: Transcription Factor Binding: tf co-factor binding;

DNA-Binding: sequence-specific

DBD Protein Group Classification: Zipper-Type Group
DBD Protein Group/Family Classification: Zipper-Type Group / Leucine Zipper Family
Homolog Cluster(s): 107503

Evidence:

Pubmed ID Function Species Evidence Strength Reviewer's Comments Reviewer
[7504176] DNA Binding Human Weak Fra1 has a conserved bZIP domain. Ability of Fra1 to bind DNA as part of a complex with c-Jun protein was confirmed by EMSA. The C terminus of nontransforming Fra1 did not function as a transcriptional activator when fused to the DNA-binding domain of GAL4. Shannan HoSui
[7791782] Other Rat Medium Fra-1 lacks a transactivation function. The entire open reading frame of Fra-1 was fused to the DNA-binding domain (first 147 amino acids) of the yeast Gal4 protein. In addition, most of the leucine zipper region of Fra-1 was deleted to prevent dimerization and subsequent transactivation by Jun partner proteins. Equivalent fusion proteins between Gal4 and c-Fos were generated for use as controls. Expression plasmids directing the synthesis of these hybrid transcription factors were transiently transfected into NIH 3T3 cells together with a reference g-globin gene and the Gal4-responsive reporter gene pfos-4. S1 nuclease analysis showed that full-length Gal4 and both c-Fos fusion proteins strongly stimulated transcription of a Gal4-responsive fos reporter gene. However, both Fra-1 fusion proteins, Gal4�Fra-1 and Gal4�Fra-1-Dzip, were unable to activate Gal4-dependent transcription, as was the polypeptide Gal4 consisting of only the DNA-binding domain. Failed synthesis or instability of the Gal4�Fra-1 proteins was ruled out: all three proteins, were efficiently expressed in transiently transfected COS-7 cells, as shown by the EMSA analysis, expression of the Gal4�Fra-1 fusion proteins efficiently interfered with transactivation by the full-length Gal4 protein in competition experiments, in contrast to the situation observed with the hybrid Gal4-cFos transcription factors. Shannan HoSui
[15608675] DNA Binding Human Strong Inducible MCF7-Fra-1 cells were analysed for their ability to form AP-1 complexes by electrophoretic mobility shift assays using a consensus TRE oligonucleotide. Sp1 DNA-binding activity was tested in parallel as a control of the efficiency of nuclear protein extraction in the different cell extracts. Higher protein binding to TRE was detected in MCF7-Fra-1 cells in the absence of doxycycline than in the presence of doxycycline or in the parental MCF7t cells. In addition, AP-1-mediated transcription, measured by transient transfection of reporter constructs containing four AP-1-binding sites, was increased by about threefold.

Inhibition of Fra-1 expression in the ER- MDA-MB231 cell line. Fra-1 expression was specifically inhibited in ER- breast cancer cells by RNA interference. The Fra-1 signal level was decreased by more than 98% in cells transfected by Fra-1-specific siRNA compared to control. C-fos expression, which was not modulated by Fra-1 overexpression in MCF7 cells, was weakly but reproducibly reduced by Fra-1 siRNA. Actin and Fra-2 content was unaffected, thus demonstrating the specificity of the silencing and the lack of general toxicity on the cells. Fra-1 extinction in MDA-MB231 cells decreased binding to the AP-1-specific DNA sequence and led to a fivefold inhibition of AP-1-mediated transcription. Moreover, Fra-1 siRNA rapidly changed the morphological appearance of the cells.

Shannan HoSui
Additional Reviewer Comments:
Reviewer: Shannan HoSui

Fra-1 is one component of the AP-1 transcription factor, which consists of a complex mixture of polypeptides that are encoded by the immediate-early genes of the fos and jun families. The three Jun proteins (c-Jun, JunB, and JunD) and the four Fos family members (c-Fos, FosB, Fra-1, and Fra-2) share a homologous region containing the basic DNA-binding domain and the leucine zipper dimerization motif. Jun proteins are able to form homo- and heterodimers, while Fos proteins are only capable of forming heterodimeric complexes with Jun proteins. Both Jun and Fos contribute to the transactivation function of the AP-1 complex, which stimulates transcription by binding to AP-1 consensus sequences (TGA G/C TCA) in enhancer and promoter regions. There is conflicting evidence regarding Fra-1's transactivation function. DNA binding has been demonstrated via EMSA.


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Facts about Fosl1 14283RDF feed
Gene description fos-like antigen 1  +
Gene id 14,283  +
Gene judgment TF Gene  +
Gene symbol fosl1  +, AW538199  +, fra-1  +, and Fra1  +
Gene taxonomy Transcription Factor Binding: tf co-factor binding  +, and DNA-Binding: sequence-specific  +
Homolog cluster 107,503  +
Protein family 3 Zipper-Type Group/21 Leucine Zipper Family  +
Protein group 3 Zipper-Type Group   +
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