The Vitamin D Receptor Interacts with General Transcription Factor IIB

MacDonald, Paul N.; Sherman, David R.; Dowd, Diane R.; Jefcoat, Stephen C.; DeLisle, Robert Kirk

doi:10.1074/jbc.270.9.4748

Cited by 154 publications

(86 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Interactions of TFIIB with transcription factors, including nuclear hormone receptors, have been reported (42)(43)(44)(45)(46)(47)(48)(49)(50). The ER was found to associate with various components of the preinitiation complex, including the TATA-binding protein, TFIIB, and its associated factor TAF II 30 (42,49), and to have direct interaction with TFIIB through its DBD (42,50).…”

Section: Discussionmentioning

confidence: 99%

A Novel Estradiol/Estrogen Receptor α-dependent Transcriptional Mechanism Controls Expression of the Human Prolactin Receptor

Dong

Tsai‐Morris

Dufau

2006

Journal of Biological Chemistry

View full text Add to dashboard Cite

2 -activated transcriptional expression of the hPRLR through PIII. Estradiol produced in breast stroma and adipose tissue, which are major sources of estrogen in post-menopausal women, could up-regulate hPRLR gene expression and stimulate breast tumor growth. Prolactin (PRL),2 a hormone of the lactogen/cytokine family, is produced in the anterior pituitary gland and exerts diverse cellular actions through its transmembrane receptors (PRLR) in several target tissues. Prolactin is a major factor in the proliferation and differentiation of breast epithelium and is the primary hormone in the stimulation and maintenance of lactation. Prolactin is a tumor promoter in rodents (1, 2) and has been implicated in the development of breast cancer. The hPRLR has several forms, including long form (stimulatory) and short form(s) (inhibitory) (3, 4), which are expressed in normal and tumoral breast tissue and in most human breast cancer cells (5-7), and prolactin exhibits synergistic actions with estrogens on the proliferation of these cells (8). There is local production of PRL in mammary epithelial cells, and increased expression of the PRLR long form occurs in a significant number of human mammary tumors (9 -12). A lower ratio of short (inhibitory forms)/long (activating form) receptors reported in breast tumor tissues could cause unopposed prolactin-mediated stimulatory actions of the long form and may contribute to breast tumor development and progression (7). Moreover, the PRL antagonist G129R was reported to cause apoptosis in breast cancer cells (8, 13). These findings, and the correlation between serum PRL and the incidence and progression of breast tumors (11,12,14), indicate that PRL has a role in human breast cancer. Stromal and adipose tissue are the major sources of estrogen in post-menopausal women, and could exert paracrine control of prolactin and prolactin receptor expression in adjacent mammary epithelial cells.Our previous studies on the hPRLR gene revealed its complex 5Ј genomic structure, with multiple (six) alternative non-coding exons 1 and promoter utilization (15,16). These include the preferentially utilized, generic promoter 1/exon-1 (PIII/hE1 3 ), which is also present in rat and mouse, and five human specific exon-1/promoters (hE1 N1-5 ) (15-17). These forms were found to be expressed in breast cancer cells, and variably in other tissues (16). Quantitative competitive reverse transcriptase-PCR analysis showed that E 2 induced increases of PRLR non-coding exon-1 hE1 3 (generic) mRNA transcripts directed by promoter III (hPIII) in breast cancer cells. Also, in transfection studies E 2 activated the hPIII promoter (18). This promoter contains functional Sp1 and C/EBP sites that bind Sp1/Sp3 and C/EBP␤, respectively (16,19). The lack of a formal ERE in the hPIII promoter suggested that the effect of estradiol is mediated through association of the activated ER with relevant DNA binding transfactors. Thus, although there is not a classical ERE within the hPRLR promoter/5Ј-flanking region of hPIII, our ...

show abstract

Section: Discussionmentioning

confidence: 99%

A Novel Estradiol/Estrogen Receptor α-dependent Transcriptional Mechanism Controls Expression of the Human Prolactin Receptor

Dong

Tsai‐Morris

Dufau

2006

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Another possible mechanism could involve independent binding of the protein complexes to each VDRE, with synergism resulting from an interaction of these complexes with the basal transcription machinery (43,44). Of possible relevance to this latter mechanism is the demonstration that VDR can interact with the general transcription factor TFIIB (45).…”

Section: Discussionmentioning

confidence: 99%

Transcriptional Synergism between Vitamin D-responsive Elements in the Rat 25-Hydroxyvitamin D3 24-Hydroxylase (CYP24) Promoter

Kerry

Dwivedi

Hahn

et al. 1996

Journal of Biological Chemistry

115

View full text Add to dashboard Cite

The hormone 1,25-dihydroxyvitamin D 3 (1,25-(OH) 2 D 3 1 or calcitriol) is a pleiotropic secosteroid that functions in the regulation of calcium homeostasis, cellular differentiation and proliferation, and immune function (1-5). Nuclear actions of 1,25-(OH) 2 D 3 involve the transcriptional regulation of gene expression, which is mediated by the vitamin D receptor (VDR), a ligand-activated transcription factor that belongs to the nuclear receptor superfamily (1, 6 -10). Activated VDR can bind as either a homodimer or a heterodimeric complex to a DNA sequence known as the vitamin D-responsive element (VDRE) present in the promoter of target genes (11-13). Heterodimers consisting of VDR and retinoid X receptor (RXR) are widely documented (12), although VDR heterodimeric complexes have also been demonstrated for both the retinoic acid receptor (14, 15) and the thyroid hormone receptor (16). Vitamin D-responsive elements generally display a binding motif that consists of two imperfect, direct repeat hexameric sequences (i.e. halfsites) that are separated by 3 bp or, more rarely, by 6 bp; these VDREs are referred to as DR-3 and DR-6, respectively (12).Metabolic inactivation of 1,25-(OH) 2 D 3 and conversion to water-soluble calcitroic acid occurs through the C-24 oxidation pathway. The initial step in this pathway involves the 24-hydroxylation of 1,25-(OH) 2 D 3 by the mitochondrial enzyme 25-hydroxyvitamin D 3 24-hydroxylase (CYP24) (17, 18). Rats fed a normal diet express a low level of CYP24, predominantly in the kidney. However, the enzyme can be substantially induced in kidney and intestine (19 -23) and various other cells (24 -29) by 1,25-(OH) 2 D 3 treatment. Up-regulation of CYP24 expression (19 -23) increases the metabolic clearance of 1,25-(OH) 2 D 3 , and, thereby, feedback regulates the hormone's ambient and cellular levels (17, 18). The mechanism whereby 1,25-(OH) 2 D 3 acts to modulate cellular CYP24 expression is of fundamental importance to understanding the hormone's role in health and disease.Molecular regulatory studies of CYP24 gene expression by 1,25-(OH) 2 D 3 are in progress and promoter analysis data for rat (14, 30 -33) and human (34) have been reported. In the rat CYP24 gene promoter, three VDREs on the antisense strand have been identified. We have previously defined the proximal VDRE (30) in its native promoter context, while the two more distal VDREs have been tested by fusing to a heterologous promoter (14, 31). To date, however, the functionality of the VDREs has not been verified in the context of the native CYP24 promoter, and there is no direct information available regarding the contribution of each VDRE to vitamin D induction or whether there is a cooperative interaction between the response elements. These issues are addressed in the current investigation, in which mutagenic constructs of the rat CYP24 promoter have been used in transient gene expression and gel mobility shift analysis. Construction of Mutant Clones-A 365-bp PvuII/StuI fragment containing 298 bp of 5Ј-flanking se...

show abstract

“…17 Another possibility for the observed associations is that different VDR genotypes may differentially interact with vitamin D response elements (VDRE) that could lead to altered ability to transcriptionally regulate VDR target genes. [43][44][45][46] Less is known about the role of androgens in the etiology of colorectal cancer than vitamin D or VDR, although studies in rats suggest that androgens work as promoters in the development of colon cancer. 47 Androgen receptors are also expressed in colon tissue, and changes acquired in the length of the CAG repeat of the AR gene in colon tumors have been detected.…”

Section: Discussionmentioning

confidence: 99%

Associations between vitamin D, vitamin D receptor gene and the androgen receptor gene with colon and rectal cancer

Slattery

Sweeney

Murtaugh

et al. 2006

Intl Journal of Cancer

View full text Add to dashboard Cite

The transcriptional activity of the vitamin D receptor (VDR) gene is regulated, at least in part, by the androgen receptor (AR) gene. We evaluate how the number of polyglutamine (CAG) repeats of the AR gene influence colorectal cancer in conjunction with vitamin D, sunshine exposure and VDR. Studies of colon (1,580 cases and 1,968 controls) and rectal (797 cases and 1,016 controls) cancer were used. Vitamin D intake and average hours of sunshine exposure interacted with AR genotype in men. Men with low vitamin D intake or low levels of sunshine exposure who had 231 CAG repeats of the AR gene had the greatest risk of colon cancer. ORs for men with 23 or more CAG repeats of the AR gene and in the lowest tertile of vitamin D intake or sunshine exposure were 1.71 (95% CI 1.14, 2.56) and 1.51 (95% CI 1.09, 2.09). Men with high levels of sunshine exposure were at reduced risk of developing rectal cancer if they had 23 or more CAG repeats (OR 0.62 95% CI 0.39, 0.97) than if they had fewer than 23 CAG repeats. The FF genotype of the Fok1 VDR gene was associated with reduced risk of colon cancer among women with any allele of 231 CAG repeats (OR 0.62 95% CI 0.44, 0.88), whereas men with the LL/bb VDR genotypes were at reduced risk of rectal cancer if they also had 231 CAG repeats (OR 0.71 95% CI 0.48, 1.05) relative to men with fewer than 23 CAG repeats of the AR gene. These data provide support for the role of vitamin D and sunshine exposure in the etiology of colorectal cancer and suggest that AR gene may modulate the association. Vitamin D has been associated inconsistently with colorectal cancer. 10 Differences in relative risk could stem from many sources, including sunshine, a major source of vitamin D, not being considered as part of the risk factor equation. Several investigators have studied sunshine exposure independently to better understand the associations between vitamin D and colorectal cancer. 11-13 Polymorphisms of the VDR gene have also been studied in conjunction with colorectal cancer and adenomas, since it may play a key role in vitamin D signaling, which could further influence colorectal cancer risk. [14][15][16][17][18][19] Polymorphisms of the VDR gene that have been studied include a poly A repeat at the 3 0 untranslated region (3 0 UTR) of the gene, 2 polymorphisms at intron 8 (Bsm I and Apa I) and 1 in exon 9 (Taq I) that are in linkage-disequilibrium with each other. 17,20 These polymorphisms, either alone or in combination, have been associated with increased mRNA expression of the VDR gene and increased serum levels of 1,25-dihydroxy vitamin D. 21,22 At the start site of the gene, a polymorphism detected with a Fok I digest has also been studied and has been shown to be not in linkage disequilibrium with the other variants. 17 A study conducted in human fibroblast cell lines found higher vitamin D hormone activity for the F allele than for the f allele. 23 One study showed that the ff genotype of the Fok I polymorphism increased risk of colorectal cancer, 18 whereas another showed that it w...

show abstract

The Vitamin D Receptor Interacts with General Transcription Factor IIB

Cited by 154 publications

References 27 publications

A Novel Estradiol/Estrogen Receptor α-dependent Transcriptional Mechanism Controls Expression of the Human Prolactin Receptor

A Novel Estradiol/Estrogen Receptor α-dependent Transcriptional Mechanism Controls Expression of the Human Prolactin Receptor

Transcriptional Synergism between Vitamin D-responsive Elements in the Rat 25-Hydroxyvitamin D3 24-Hydroxylase (CYP24) Promoter

Associations between vitamin D, vitamin D receptor gene and the androgen receptor gene with colon and rectal cancer

Contact Info

Product

Resources

About