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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

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	11q13.1      Physical location : 65.659.691 - 65.667.997
Synonym name	FOS antigen-like 1
	FOS-like antigen-1
	fos-related antigen 1
Synonym symbol(s)	FOSR1, FRA1, fra-1, FRA

DNA

TYPE	functioning gene
STRUCTURE	8.31 kb     4 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter
text structure	two critical elements of promoter, the upstream TPA response element (TRE) and the serum response element (SRE), are necessary for its induction in response to phorbol esters in pulmonary epithelial cell lines (Adiseshaiah 2008 )

MAPPING

cloned

Y

linked

N

status

confirmed

Map	cen - D11S4205 - D11S1883 - FOSL1 - D11S1889 - D11S4155 - qter

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_005438 4 - 1668 NP_005429 - 271 - Adiseshaiah (2008)

EXPRESSION

Type

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive liver         Endocrine pancreas       predominantly Lymphoid/Immune lymph node

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / Hematopoietic bone marrow       Epithelial secretory glandular endocrine predominantly

cells

System Cell Pubmed Species Stage Rna symbol Skeleton osteoclast

cell lineage
cell lines	High Fra-1 levels are associated with enhanced tumour cell proliferation, survival, migration and invasion
fluid/secretion

at STAGE

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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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