RGD Reference Report - Physical and functional interaction between the vitamin D receptor and hairless corepressor, two proteins required for hair cycling. - Rat Genome Database

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Physical and functional interaction between the vitamin D receptor and hairless corepressor, two proteins required for hair cycling.

Authors: Hsieh, JC  Sisk, JM  Jurutka, PW  Haussler, CA  Slater, SA  Haussler, MR  Thompson, CC 
Citation: Hsieh JC, etal., J Biol Chem. 2003 Oct 3;278(40):38665-74. Epub 2003 Jul 7.
RGD ID: 1599578
Pubmed: PMID:12847098   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M304886200   (Journal Full-text)

Both the vitamin D receptor (VDR) and hairless (hr) genes play a role in the mammalian hair cycle, as inactivating mutations in either result in total alopecia. VDR is a nuclear receptor that functions as a ligand-activated transcription factor, whereas the hairless gene product (Hr) acts as a corepressor of both the thyroid hormone receptor (TR) and the orphan nuclear receptor, RORalpha. In the present study, we show that VDR-mediated transactivation is strikingly inhibited by coexpression of rat Hr. The repressive effect of Hr is observed on both synthetic and naturally occurring VDR-responsive promoters and also when VDR-mediated transactivation is augmented by overexpression of its heterodimeric partner, retinoid X receptor. Utilizing in vitro pull down methods, we find that Hr binds directly to VDR but insignificantly to nuclear receptors that are not functionally repressed by Hr. Coimmunoprecipitation data demonstrate that Hr and VDR associate in a cellular milieu, suggesting in vivo interaction. The Hr contact site in human VDR is localized to the central portion of the ligand binding domain, a known corepressor docking region in other nuclear receptors separate from the activation function-2 domain. Coimmunoprecipitation and functional studies of Hr deletants reveal that VDR contacts a C-terminal region of Hr that includes motifs required for TR and RORalpha binding. Finally, in situ hybridization analysis of hr and VDR mRNAs in mouse skin demonstrates colocalization in cells of the hair follicle, consistent with a hypothesized intracellular interaction between these proteins to repress VDR target gene expression, in vivo.



Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
HrRatnuclear vitamin D receptor binding  IPIVDR (Homo sapiens) RGD 
HrRatprotein-containing complex binding  IDAVDR (Homo sapiens)heterooligomerization and binds the vitamin D receptor-retinoid X receptor complexRGD 

Objects Annotated

Genes (Rattus norvegicus)
Hr  (HR, lysine demethylase and nuclear receptor corepressor)


Additional Information