RGD Reference Report - The alpha1-fetoprotein locus is activated by a nuclear receptor of the Drosophila FTZ-F1 family. - Rat Genome Database

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The alpha1-fetoprotein locus is activated by a nuclear receptor of the Drosophila FTZ-F1 family.

Authors: Galarneau, L  Pare, JF  Allard, D  Hamel, D  Levesque, L  Tugwood, JD  Green, S  Belanger, L 
Citation: Galarneau L, etal., Mol Cell Biol 1996 Jul;16(7):3853-65.
RGD ID: 68248
Pubmed: PMID:8668203   (View Abstract at PubMed)
PMCID: PMC231382   (View Article at PubMed Central)

The alpha1-fetoprotein (AFP) gene is located between the albumin and alpha-albumin genes and is activated by transcription factor FTF (fetoprotein transcription factor), presumed to transduce early developmental signals to the albumin gene cluster. We have identified FTF as an orphan nuclear receptor of the Drosophila FTZ-F1 family. FTF recognizes the DNA sequence 5'-TCAAGGTCA-3', the canonical recognition motif for FTZ-F1 receptors. cDNA sequence homologies indicate that rat FTF is the ortholog of mouse LRH-1 and Xenopus xFF1rA. Rodent FTF is encoded by a single-copy gene, related to the gene encoding steroidogenic factor 1 (SF-1). The 5.2-kb FTF transcript is translated from several in-frame initiator codons into FTF isoforms (54 to 64 kDa) which appear to bind DNA as monomers, with no need for a specific ligand, similar KdS (approximately equal 3 x 10(-10) M), and similar transcriptional effects. FTF activates the AFP promoter without the use of an amino-terminal activation domain; carboxy-terminus-truncated FTF exerts strong dominant negative effects. In the AFP promoter, FTF recruits an accessory trans-activator which imparts glucocorticoid reactivity upon the AFP gene. FTF binding sites are found in the promoters of other liver-expressed genes, some encoding liver transcription factors; FTF, liver alpha1-antitrypsin promoter factor LFB2, and HNF-3beta promoter factor UF2-H3beta are probably the same factor. FTF is also abundantly expressed in the pancreas and may exert differentiation functions in endodermal sublineages, similar to SF-1 in steroidogenic tissues. HepG2 hepatoma cells seem to express a mutated form of FTF.



Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Nr5a2Ratdouble-stranded DNA binding  IDA  RGD 
Nr5a2Ratnuclear receptor activity  IDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Nr5a2  (nuclear receptor subfamily 5, group A, member 2)

Objects referenced in this article
Gene Nr5a2 nuclear receptor subfamily 5, group A, member 2 Mus musculus

Additional Information