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FLASH GENE
Symbol FOSL1 contributors: mct/npt/shn - updated : 04-12-2012
HGNC name FOS-like antigen 1
HGNC id 13718
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • one bzip domain
    • mono polymer heteromer , dimer
    HOMOLOGY
    interspecies ortholog to Fosl1, Mus musculus
    ortholog to Fosl1, Rattus norvegicus
    ortholog to FOSL1, Pan troglodytes
    ortholog to fosl1a, Danio rerio
    Homologene
    FAMILY
  • FOS family of transcription factors
  • Activator Protein-1 (AP-1) transcription factor superfamily
    • CATEGORY regulatory , transcription factor , protooncogene
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic,microsome
    intracellular,nucleus
    basic FUNCTION
  • involved in the cell proliferation, differentiation, and transformation
  • may likely play an important role in the maintenance/progression of malignant gliomas
  • in regulating bone mass through bone matrix production by osteoblasts and chondrocytes
  • inhibits inducible IL-8 transcription
  • like FOS, belongs to a small group of proteins that may, under certain circumstances, undergo ubiquitin-independent degradation by the proteasome (Basbous 2007)
  • functions as a positive transcriptional regulator in human keratinocytes
  • key regulator of cell motility, invasiveness, growth and survival of tumor cells
  • might play a role in the progression and prognosis of non-small-cell lung cancer
  • modulates JUN dimer composition by promoting the accumulation of c-Jun in response to oncogenic RAS signaling
  • key downstream effector of the PI3K/AKT signaling pathway responsible for development of trophoblast lineages integral to establishing the maternal-fetal interface
  • constitutes a regulatory module with microRNA-138 that may play an important role in cancer initiation and progression
    • CELLULAR PROCESS cell life, differentiation
    cell life, proliferation/growth
    nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS development , immunity/defense , carcinogenesis
    PATHWAY
    metabolism
    signaling
    a component
  • forming heterodimers, the AP-1 complex with proteins of the JUN family
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • USF
  • histone deacetylase-1
  • TXLNG regulate later osteoblast function through inhibition of FOSL1
  • posttranslational regulator of c-Jun stability in RAS transformation
  • occupy regions of the MMP9 promoter in trophoblast cells critical for the regulation of MMP9 gene expression
    • cell & other
    REGULATION
    activated by Human T-cell leukemia virus type 1 Tax
    induced by TNFSF11(RANKL)
    Other transcriptional target of C.Fos during osteoclast differentiation
    TBP-1 and 19S proteasomal subunit
    down-regulated by microRNA-138
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in breast cancer in progression
    tumoral     --over  
    in pancreatic cancer
    tumoral     --low  
    in non-small-cell lung cancer with poor survival (Ma 2009)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
  • target for therapeutic interventions in malignant gliomas
  • gene ablation can suppress the invasive phenotypes of many tumor cell lines
  • potentially useful in pancreatic tumor targeting or as tumor markers
  • lethality of fra-1-knockout mice can be rescued by specific deletion of Fra-1 only in the mouse embryo
  • autoregulatory loop between JUN and FOSL1 might represent an important determinant for the increased JUN activity and a novel target for therapeutic intervention in tumorigenesis
    • ANIMAL & CELL MODELS
  • Ectopic expression of the transcription factor Fra-1 in transgenic mice leads to osteosclerosis
  • fra-1-knockout mice die in utero likely due to placental defects
  • Mice lacking Fra-1 (fra-1(delta/delta)) are viable and develop osteopenia, a low bone mass disease