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PMID:15143342

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Citation

Steffensen, KR, Holter, E, Båvner, A, Nilsson, M, Pelto-Huikko, M, Tomarev, S and Treuter, E (2004) Functional conservation of interactions between a homeodomain cofactor and a mammalian FTZ-F1 homologue. EMBO Rep. 5:613-9

Abstract

Nuclear receptors are master regulators of metazoan gene expression with crucial roles during development and in adult physiology. Fushi tarazu factor 1 (FTZ-F1) subfamily members are ancient orphan receptors with homologues from Drosophila to human that regulate diverse gene expression programs important for developmental processes, reproduction and cholesterol homeostasis in an apparently ligand-independent manner. Thus, developmental and tissue-specific cofactors may be particularly important in modulating the transcriptional activities of FTZ-F1 receptors. In Drosophila, the homeodomain protein Fushi tarazu acts as a cofactor for FTZ-F1 (NR5A3), leading to the hypothesis that a similar type of homeodomain cofactor-nuclear receptor relationship might exist in vertebrates. In this study, we have identified and characterized the homeodomain protein Prox1 as a co-repressor for liver receptor homologue 1 (LRH1/NR5A2), a master regulator of cholesterol homeostasis in mammals. Our study suggests that interactions between LRH1 and Prox1 may fulfil roles both during development of the enterohepatic system and in adult physiology of the liver.

Links

PubMed PMC1299067 Online version:10.1038/sj.embor.7400147

Keywords

Animals; Cell Line; DNA-Binding Proteins/analysis; DNA-Binding Proteins/genetics; DNA-Binding Proteins/metabolism; Down-Regulation/physiology; Histone Deacetylases/analysis; Histone Deacetylases/metabolism; Homeodomain Proteins/analysis; Homeodomain Proteins/genetics; Homeodomain Proteins/metabolism; Humans; Liver/chemistry; Liver/metabolism; Protein Interaction Mapping; Protein Structure, Tertiary; RNA, Messenger/analysis; RNA, Messenger/metabolism; Receptors, Cytoplasmic and Nuclear/analysis; Receptors, Cytoplasmic and Nuclear/genetics; Receptors, Cytoplasmic and Nuclear/metabolism; Steroidogenic Factor 1; Tissue Distribution; Transcription Factors/genetics; Tumor Suppressor Proteins

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:NR5A2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q92786

F

Seeded From UniProt

complete

HUMAN:NR5A2

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:PROX1

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:PROX1

enables

GO:0016922: nuclear receptor binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O00482

F

Seeded From UniProt

complete

HUMAN:PROX1

enables

GO:0001227: DNA-binding transcription repressor activity, RNA polymerase II-specific

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:PROX1

enables

GO:0050693: LBD domain binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O00482

F

Seeded From UniProt

complete

HUMAN:PROX1

involved_in

GO:0045892: negative regulation of transcription, DNA-templated

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:NR5A2

part_of

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:NR5A2

involved_in

GO:0045893: positive regulation of transcription, DNA-templated

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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