scholarly journals Ternary Complexes and Cooperative Interplay between NCoA-62/Ski-interacting Protein and Steroid Receptor Coactivators in Vitamin D Receptor-mediated Transcription

2001 ◽  
Vol 276 (44) ◽  
pp. 40614-40620 ◽  
Author(s):  
Chi Zhang ◽  
Troy A. Baudino ◽  
Diane R. Dowd ◽  
Hisashi Tokumaru ◽  
Wen Wang ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Steroid Receptor ◽  
Ternary Complexes ◽  
Interacting Protein ◽  
Steroid Receptor Coactivators

scholarly journals Hairless Suppresses Vitamin D Receptor Transactivation in Human Keratinocytes

Endocrinology ◽  
2006 ◽  
Vol 147 (1) ◽  
pp. 314-323 ◽  
Author(s):  
Zhongjian Xie ◽  
Sandra Chang ◽  
Yuko Oda ◽  
Daniel D. Bikle
Keyword(s):  
Vitamin D ◽  
Hair Follicle ◽  
Vitamin D Receptor ◽  
Human Keratinocytes ◽  
Potential Interaction ◽  
Keratinocyte Differentiation ◽  
Mobility Shift ◽  
Dihydroxyvitamin D3 ◽  
Interacting Protein ◽  
Hydroxyvitamin D

The vitamin D receptor (VDR) and its ligand 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] are required for normal keratinocyte differentiation. Both the epidermis and the hair follicle are disrupted in VDR-null mice. Hairless (Hr), a presumptive transcription factor with no known ligand, when mutated, disrupts hair follicle cycling similar to the effects of VDR mutations. Hr, like VDR, is found in the nuclei of keratinocytes in both epidermis and hair follicle. To investigate the potential interaction between Hr and VDR on keratinocyte differentiation, we examined the effect of Hr expression on vitamin D-responsive genes in normal human keratinocytes. Inhibition of Hr expression in keratinocytes potentiated the induction of vitamin D-responsive genes, including involucrin, transglutaminase, phospholipase C-γ1, and 25-hydroxyvitamin D-24-hydroxylase (24-hydroxylase) by 1,25(OH)2D3. Overexpression of Hr in human keratinocytes suppressed the induction of these vitamin D-responsive genes by 1,25(OH)2D3. Coimmunoprecipitation, DNA mobility shift assays, and chromatin immunoprecipitation revealed that Hr binds to VDR in human keratinocytes. Hr binding to the VDR was eliminated by 1,25(OH)2D3, which recruited the coactivator vitamin D receptor-interacting protein 205 (DRIP205) to the VDR/vitamin D response element complex. These data indicate that Hr functions as a corepressor of VDR to block 1,25(OH)2D3 action on keratinocytes.

Vitamin D receptor gene polymorphisms and steroid receptor status among Saudi women with breast cancer

Gene ◽  
2015 ◽  
Vol 558 (2) ◽  
pp. 215-219 ◽  
Author(s):  
Dalal M. Nemenqani ◽  
Rehab A. Karam ◽  
Mona G. Amer ◽  
Tamer M. Abd El Rahman
Keyword(s):  
Breast Cancer ◽  
Vitamin D ◽  
Vitamin D Receptor ◽  
Gene Polymorphisms ◽  
Receptor Gene ◽  
Steroid Receptor ◽  
Vitamin D Receptor Gene ◽  
Receptor Status ◽  
Saudi Women ◽  
Receptor Gene Polymorphisms

scholarly journals Polyamines Modulate the Interaction between Nuclear Receptors and Vitamin D Receptor-Interacting Protein 205

2002 ◽  
Vol 16 (7) ◽  
pp. 1502-1510 ◽  
Author(s):  
Yutaka Maeda ◽  
Christophe Rachez ◽  
Leo Hawel ◽  
Craig V. Byus ◽  
Leonard P. Freedman ◽  
...  
Keyword(s):  
Vitamin D ◽  
Ligand Binding ◽  
Nuclear Receptors ◽  
Vitamin D Receptor ◽  
Binding Domain ◽  
Ligand Binding Domain ◽  
Full Length ◽  
Dependent Manner ◽  
Interacting Protein

Abstract Nuclear receptors (NR) activate transcription by interacting with several different coactivator complexes, primarily via LXXLL motifs (NR boxes) of the coactivator that bind a common region in the ligand binding domain of nuclear receptors (activation function-2, AF–2) in a ligand-dependent fashion. However, how nuclear receptors distinguish between different sets of coactivators remains a mystery, as does the mechanism by which orphan receptors such as hepatocyte nuclear factor 4α (HNF4α) activate transcription. In this study, we show that HNF4α interacts with a complex containing vitamin D receptor (VDR)-interacting proteins (DRIPs) in the absence of exogenously added ligand. However, whereas a full-length DRIP205 construct enhanced the activation by HNF4α in vivo, it did not interact well with the HNF4α ligand binding domain in vitro. In investigating this discrepancy, we found that the polyamine spermine significantly enhanced the interaction between HNF4α and full-length DRIP205 in an AF-2, NR-box-dependent manner. Spermine also enhanced the interaction of DRIP205 with the VDR even in the presence of its ligand, but decreased the interaction of both HNF4α and VDR with the p160 coactivator glucocorticoid receptor interacting protein 1 (GR1P1). We also found that GR1P1 and DRIP205 synergistically activated HNF4α-mediated transcription and that a specific inhibitor of polyamine biosynthesis, α-difluoromethylornithine (DFMO), decreased the ability of HNF4α to activate transcription in vivo. These results lead us to propose a model in which polyamines may facilitate the switch between different coactivator complexes binding to NRs.

scholarly journals Mapping the Domains of the Interaction of the Vitamin D Receptor and Steroid Receptor Coactivator-1

1998 ◽  
Vol 12 (1) ◽  
pp. 57-65 ◽  
Author(s):  
Rajbir K. Gill ◽  
Loretta M. Atkins ◽  
Bruce W. Hollis ◽  
Norman H. Bell
Keyword(s):  
Vitamin D ◽  
Mutation Analysis ◽  
Vitamin D Receptor ◽  
Deletion Mutant ◽  
Active Form ◽  
Steroid Receptor ◽  
Deletion Mutation ◽  
Biologically Active ◽  
Dependent Manner ◽  
Steroid Receptor Coactivator

Abstract The vitamin D receptor (VDR) binds to the vitamin D response element (VDRE) and mediates the effects of the biologically active form of vitamin D, 1,25-dihydroxyvitamin D3[ 1,25-(OH)2D3], on gene expression. The VDR binds to the VDRE as a heterodimeric complex with retinoid X receptor. In the present study, we have used a yeast two-hybrid system to clone complementary DNA that codes for VDR-interacting protein(s). We found that the human steroid receptor coactivator-1 (SRC-1) interacts with the VDR in a ligand-dependent manner, as demonstrated by β-galactosidase production. The interaction of the VDR and the SRC-1 takes place at physiological concentrations of 1,25(OH)2D3. A 48.2-fold stimulation of β-galactosidase activity was observed in the presence of 10−10m 1,25-(OH)2D3. In addition, a direct interaction between the ligand-activated glutathione-S-transferase-VDR and 35S-labeled SRC-1 was observed in vitro. Deletion-mutation analysis of the VDR established that the ligand-dependent activation domain (AF-2) of the VDR is required for the interaction with SRC-1. One deletion mutant, pGVDR-(1–418), bound the ligand but failed to interact with the SRC-1, whereas another deletion mutant, pGVDR-(1–423), bound the ligand and interacted with the SRC-1. We demonstrated that all the deletion mutants were expressed as analyzed by a Gal4 DNA-binding domain antibody. Deletion mutation analysis of the SRC-1 demonstrated that 27 amino acids (DPCNTNPTPMTKATPEEIKLEAQS-QFT) of the SRC-1 are essential for interaction with the AF-2 motif of the VDR.

Sign in / Sign up

Export Citation Format

Share Document