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C Carlberg

Publications and source records attributed to C Carlberg.

At least 73 records · Page 4Linked to original sources
PubMed1995

Mechanisms of nuclear signalling by vitamin D3. Interplay with retinoid and thyroid hormone signalling.

Hormones that act through nuclear receptors contribute to vertebrate development and homeostasis by serving as biological signals to control cellular growth and differentiation. Their response pathways must meet two requirements, which can be contradictory: they must be highly specific for a given signal, but at the same time they have to be flexible, allowing different responses under different physiological conditions. The current model for nuclear signalling of vitamin D3 (calcitriol), thyroid hormone and retinoic acid seems to be too simple to solve the specificity puzzle. Therefore, an advanced model is proposed that combines recent findings on the structure of hormone response elements, the promiscuous dimerization of the receptors for vitamin D3, thyroid hormone and retinoids and the heterodimer polarity. Special attention is taken on the mechanism of vitamin D3 signalling, where at least 14 different pathways are differentiated.

Animals↗
PubMed1995

[Urinary albumin excretion by patients with type 2 diabetes mellitus. Effect of blood pressure and metabolic regulation].

BACKGROUND: There is still controversy as to whether increased urinary albumin excretion (UAE) in patients with type 2 diabetes mellitus may have similar pathognomonic relevance as in type 1 diabetes and whether improved metabolic control may beneficially influence increased UAE in type 2 diabetic patients to the same extent as in type 1 diabetic patients. PATIENTS AND METHODS: In a cross-sectional study in 234 patients with type 2 diabetes (age, 64 +/- 1 years, known duration of diabetes, 14 +/- 1 years) UAE, haemoglobin A1, blood pressure, cholesterol, triglyceride and creatinine levels were measured and signs of retinopathy were evaluated. Results were compared with the findings in 247 patients with type 1 diabetes (age, 39 +/- 1 years, duration of diabetes, 15 +/- 1 years). In a longitudinal study, UAE, haemoglobin A1, blood pressure, cholesterol, triglyceride and creatinine levels were measured in 41 patients with type 2 diabetes and secondary failure of oral hypoglycemic treatment (age, 62 +/- 1 years, known duration of diabetes, 11 +/- 1 years) before and after 2-year insulin treatment. RESULTS: In the cross-sectional study, 39% of the type 2 diabetic patients had increased UAE, 27% had microalbuminuria, in contrast to 21% and 14%, respectively, of the type 1 diabetic patients (p < 0.01). In type 2 diabetes, macroalbuminuria was detected after an average of 15 +/- 2 years in contrast to 25 +/- 2 years in type 1 diabetes (p < 0.01). In comparison to macroalbuminuric type 1 diabetic patients, macroalbuminuric type 2 diabetes patients exhibited a lower prevalence of renal insufficiency (30 vs. 53%, p < 0.05) as well as of retinopathy (59 vs. 88%, p < 0.05), but a higher prevalence of hypertension (93 vs. 65%, p < 0.05) as well as of hyperlipidaemia (p < 0.01). There was a significant relation between UAE and haemoglobin A1 in patients with type 1 diabetes (p < 0.01) which could not be demonstrated in type 2 diabetic patients. In the longitudinal study, UAE fell from 86 +/- 28 to 51 +/- 16 mg/24 hours (p < 0.05) and the prevalence of UAE of more than 30 mg/24 hours decreased from 45 to 25% (p < 0.05) after 2-year insulin treatment, while blood pressure remained constant and haemoglobin A1 fell from 12.3 +/- 0.4 to 8.8 +/- 0.3% (p < 0.01). In comparison to patients with normal or normalized UAE after 2 years, patients with persistently elevated UAE had more advanced kidney disease (p < 0.05), more pronounced insulin resistance and a higher prevalence of calculated mean arterial blood pressure above 103 mm Hg and of haemoglobin A1 higher than 9% (normal, < 7%) in the course of the study (p < 0.05). CONCLUSION: In patients with both type 2 and type 1 diabetes mellitus, increased UAE is a marker for the nephropathy-related sequelae of long-term hyperglycaemia. In type 2 diabetic patients, however, the frequently pre-existing hypertension as well as other disease mechanism of the "metabolic syndrome" ("syndrome X") may additionally determine course and progression of diabetic kidney disease.

Aged↗
PubMed1995

The nuclear receptor for melatonin represses 5-lipoxygenase gene expression in human B lymphocytes.

The two subtypes of retinoid Z receptor (RZR alpha and beta) and the three splicing variants of retinoid orphan receptor (ROR alpha 1, alpha 2, and alpha 3) form a subfamily within the superfamily of nuclear hormone receptors. Very recently we found that the pineal gland hormone melatonin is a natural ligand of RZR alpha and RZR beta. Ligand-induced transcriptional control is therefore proposed to mediate physiological functions of melatonin in the brain where RZR beta is expressed, but also in peripheral tissues, where RZR alpha was found. However, no natural RZR responding genes have been identified yet. Here, we report that a response element in the promoter of 5-lipoxygenase binds specifically RZR alpha and ROR alpha 1, but not ROR alpha 2 and alpha 3. 5-Lipoxygenase is a key enzyme in the biosynthesis of leukotrienes, which are known to be allergic and inflammatory mediators. We could show that the activity of the whole 5-lipoxygenase promoter as well as of the RZR response element fused to the heterologous thymidine kinase promoter could be repressed by melatonin. The hormone down-regulated the expression of 5-lipoxygenase about 5-fold in B lymphocytes, which express RZR alpha. In contrast, 5-lipoxygenase mRNA levels were not affected in differentiated monocytic and granulocytic cell lines, which do not express RZR alpha. This indicates that 5-lipoxygenase is the first natural RZR alpha responding gene. Furthermore, our results open up a new perspective in understanding the involvement of melatonin in inflammatory and immunological reactions.

Arachidonate 5-Lipoxygenase↗
PubMed1995

Transcriptional activation of the nuclear receptor RZR alpha by the pineal gland hormone melatonin and identification of CGP 52608 as a synthetic ligand.

Many important physiological functions are controlled by hormones via binding and activating members of the nuclear receptor superfamily. This group of structurally related transcription factors also includes a still growing number of orphan receptors for which no ligand is known so far. The identification of ligands for orphan receptors is a key to understanding their physiological role, as has been successfully shown for retinoid X receptors and the discovery of 9-cis retinoic acid as a specific ligand. We have discovered very recently that the pineal gland hormone melatonin is a specific ligand for the brain-specific nuclear receptor RZR beta. Here we report that the alpha-subtype of RZR, RZR alpha and its splicing variant ROR alpha 1, is also a nuclear receptor for melatonin with binding specificities in the low nanomolar range. In contrast to RZR beta, RZR/ROR alpha is expressed in many tissues and cells outside the brain. We found that RZR alpha and ROR alpha 1 vary in their constitutive transactivational activity and are activated to a different extent by melatonin. Furthermore, we identified a synthetic RZR-ligand, the thiazolidine dione CGP 52608. This compound is a functional analogue of melatonin at its nuclear receptor, but does not bind to the high affinity membrane receptor for melatonin. Therefore, this specific RZR-ligand may help to differentiate between nuclear and membrane signalling of melatonin.

Animals↗
PubMed1995

The induction and functions of murine T-helper cell subsets.

Through the release of distinct sets of cytokines, Th1 and Th2 cells exert characteristic and often mutually exclusive or antagonistic immune effector functions. In the present report, we document and discuss several findings on the induction mechanisms of these cellular subtypes and present recent findings on their respective functions in vivo. The preferential induction of Th1 or Th2 cytokine patterns in mature CD4+ T cells is generally attributed to the action of cytokines. In addition, there is evidence that prolonged T-cell receptor occupancy may induce the development of the Th2 phenotype. Prolonged occupancy of the T-cell receptor provides enough autocrine interleukin-4 to permit induction of the Th2 phenotype. Both Th1 and Th2 cells may be derived from a single mature CD4+ T cell, providing strong evidence for post-thymic modulation of the T-cell cytokine profile and rendering the possibility of predetermined cytokine patterns in T cells unlikely. CD4+ Th1 cells mediate the tumor necrosis factor- and interferon-gamma-dependent classic delayed type hypersensitivity reaction. We found that Th2 cells were also capable of mediating local inflammatory reactions that depended on their prototypic lymphokine interleukin-4, and, in high tumor necrosis factor-producing mouse strains, upon tumor necrosis factor-alpha. Both Th-cell subsets induced cellular infiltrates that were not distinguishable on histologic grounds. In contrast to the widely accepted belief that only Th1 cells can mediate delayed hypersensitivity reactions, our results demonstrate that T cells with either lymphokine profile can cause tissue inflammation with leukocytic infiltrates.

Animals↗
PubMed1995

The orphan receptor family RZR/ROR, melatonin and 5-lipoxygenase: an unexpected relationship.

The orphan receptors RZR alpha, RZR beta, ROR alpha 1, RZR alpha 2, ROR alpha 3, and ROR gamma form a subfamily within the superfamily of nuclear hormone receptors. Recently, experimental evidence that the pineal gland hormone melatonin is the natural ligand for these nuclear receptors has come to light. This discovery is rather surprising, given that most people in the field believed melatonin acts exclusively through membrane receptors. However, these new findings establish a nuclear signalling pathway for melatonin, i.e., direct ligand-induced control of target gene transcription, which most probably mediates part of the physiological functions of the hormone. Interestingly, the very recently identified first RZR/melatonin responding gene, 5-lipoxygenase, is not expressed in the brain and is not involved in circadian rhythmicity, but rather acts in the periphery, mainly in myeloid cells, as one of the key enzymes of allergic and inflammatory reactions. Thus, nuclear melatonin signalling opens up a new perspective in understanding the actions of the pineal gland hormone.

Animals↗
PubMed1995

Natural vitamin D3 response elements formed by inverted palindromes: polarity-directed ligand sensitivity of vitamin D3 receptor-retinoid X receptor heterodimer-mediated transactivation.

VDR, the nuclear receptor for 1,25-dihydroxyvitamin D3 (VD), is a member of the superfamily of nuclear hormone receptors and controls multiple aspects of homeostasis, cell growth, and differentiation. VDR can function as a homodimer, but heterodimerization with the retinoid X receptor (RXR), retinoic acid receptor, or thyroid hormone receptor increases its affinity for response elements in the promoter of target genes. All natural VD response elements identified so far consist of direct repeats of a variety of hexameric core binding motifs with a preferential spacing of three nucleotides (DR3s). However, all four VD signalling pathways function also on response elements formed by inverted palindromes, although these sequences were not of natural origin. Here, we report the identification of two VD response elements consisting of inverted palindromes spaced by nine nucleotides (IP9s) in the promoters of the human calbindin D9k gene and the rat osteocalcin gene. Like most DR3-type VD response elements, both IP9s are preferentially bound by VDR-RXR heterodimers with a 5'-RXR-VDR-3' polarity, whose transcriptional activity can be enhanced by costimulation with 9-cis retinoic acid. We demonstrate that changing the response element orientation relatively to the basal promoter decreases the sensitivity of transcriptional activation by VD by about 10-fold. Our findings indicate that inverted palindromes are as functional as direct repeats. Furthermore, we suggest that the orientation of a nuclear receptor complex in relation to the basic transcriptional machinery, which is directed by heterodimer polarity and response element orientation, influences the ligand sensitivity of the respective target gene expression.

Animals↗
PubMed1994

Pineal gland hormone melatonin binds and activates an orphan of the nuclear receptor superfamily.

Nuclear orpan receptors are members of the superfamily of structurally related, ligand-inducible transcription factors for which no ligand has yet been identified. Over the past few years many nuclear orphan receptors have been cloned, but only for the retinoid X receptor (RXR) has a natural ligand (9-cis-retinoic acid) been found. Here we report the identification of melatonin as a ligand for the recently cloned orphan receptor retinoid Z receptor beta (RZR beta). We found RZR beta expression in the rat brain nearly coincident with binding sites for the pineal gland hormone melatonin (5-methoxy-N-acetyltryptamine). We show here binding and activation of RZR beta by melatonin with Kd and EC50 values in the low nanomolar range. A nuclear signaling pathway for melatonin may contribute to some of the diverse and profound effects of this hormone, for example, in the context of circadian rhythmicity.

Animals↗
PubMed1994

Identification of a vitamin D receptor homodimer-type response element in the rat calcitriol 24-hydroxylase gene promoter.

Calcitriol (1,25-dihydroxyvitamin D3, VD) controls multiple aspects of homeostasis, cell growth and differentiation by the action of its nuclear receptor (VDR), which binds to, and activates transcription from, response elements in the promoter region of its target genes. One of these target genes is calcitriol 24-hydroxylase, an enzyme that initiates the degradation of 25-dihydroxyvitamin D3 (calcidiol) and calcitriol. We screened the promoter of rat calcitriol 24-hydroxylase for potential VDR binding sites and identified a functional VD response element, between positions -250 and -233. This response element consists of two directly repeated hexameric core binding motifs spaced by six nucleotides and confers VD-dependent transactivation mediated by VDR homodimers or alternatively by heterodimers formed by VDR and retinoic acid receptor (RAR). Its structure and function are very similar to those of the homodimer-type response element of the human osteocalcin promoter.

Animals↗
PubMed1994

Vitamin D3-thyroid hormone receptor heterodimer polarity directs ligand sensitivity of transactivation.

The nuclear receptors for 1,25-dihydroxyvitamin D3 (VD) and 3,5,3'-triiodothyronine (T3), that is, VDRs and T3Rs respectively, control aspects of homeostasis, cell growth and differentiation. They activate transcription from response elements consisting of direct repeats, palindromes and inverted palindromes of a variety of hexameric core-binding motifs. VDRs bind preferentially to direct repeats spaced by three nucleotides, whereas T3Rs bind to direct repeats spaced by four nucleotides. VDRs and T3Rs can function as homodimers but heterodimerization with retinoid X or retinoic acid receptors increases their affinity for DNA in vitro and resulting transcriptional activity in vivo. We recently observed the formation of VDR-T3R heterodimers. Here we show that the polarity of the binding of such heterodimers to the VD response element of the rat 9K (relative molecular mass 9,000) calbindin gene promoter was 5'-T3R-VDR-3', whereas on the mouse 28K calbindin VD response element this polarity was reversed to 5'-VDR-T3R-3'. We also show that the ligand for the downstream receptor controls the transcriptional activity of the heterodimeric complex. Thus, polarity seems to be an important regulatory property of heterodimeric nuclear receptor complexes.

Animals↗
PubMed1994

Thyroid hormone receptor functions as monomeric ligand-induced transcription factor on octameric half-sites. Consequences also for dimerization.

The thyroid hormone (3,5,3'-triiodothyronine) receptor (T3R) belongs to the nuclear receptor superfamily of ligand-inducible transcription factors. T3Rs are known to bind as homodimers and heterodimers with retinoid X receptors (RXRs) to two hexameric half-sites in directly repeated, palindromic, and inverted palindromic orientations. The binding of T3R monomers to individual half-sites was often reported, but no clear ligand-induced transactivational activity has been shown. Here, we analyzed interactions of T3R monomers with individual half-sites of the sequence NNAGGTCA. We found that the two nucleotides 5' of the AGGTCA core half-site strongly influence T3R binding and transcriptional activity: octameric half-sites of the consensus sequence (T/C)(A/G)AGGTCA were bound by T3Rs with the highest affinity. This suggests T3R functioning also as a monomeric transcription factor like the orphan nuclear receptors NGFI-B and FTZ-F1. Moreover, we observed that the function of T3R-RXR heterodimers on response elements composed of two half-sites in a directly repeated orientation spaced by 4 nucleotides is determined in major parts by the 5'-flanking sequence of the upstream half-site. Consequently, we noted that the affinity of T3R homodimers is influenced by both 5'-flanking sequences. Our findings suggest that the binding of dimerizing receptors like T3R and other nuclear receptors to their cognate response elements is determined not only by the half-site core sequence, orientation, and number of spacing nucleotides, but also by the nucleotide sequence preceding the half-sites.

Animals↗
PubMed1994

Specificity and flexibility of vitamin D signaling. Modulation of the activation of natural vitamin D response elements by thyroid hormone.

Cellular responsiveness to 1,25-dihydroxyvitamin D3 (VD) is conferred by its intracellular receptor (VDR), which belongs to the nuclear receptor superfamily of ligand-inducible transcription factors. VDRs are known to bind to specific response elements in the promoter region of VD-regulated genes. Two types of natural VD response elements (VDREs) have been identified so far. One is bound by VDR homodimers and is found in the human osteocalcin gene promoter (DR6-type), and the other is bound by heterodimers of VDR with retinoid X receptors (RXRs) as in the mouse osteopontin promoter (DR3-type). Here, we demonstrate that VDRs directly interact in solution not only with RXR but also with retinoid acid receptors (RARs) and, interestingly, with thyroid hormone receptors (T3Rs). All three heterodimeric partners were able to enhance the in vitro DNA binding affinity of VDR as compared to VDR homodimers, but they showed different affinities for the two types of VDREs, as determined by Scatchard analysis. Moreover, functional assays showed that VDR.T3R heterodimers act differently on the two types of VDREs; on the DR3-type we observed highest induction by thyroid hormone (3,5,3'-triiodothyronine, T3) alone, whereas on a DR6-type VDRE VD and T3 together provided maximal gene activity. Our data suggest that the expression levels of VDRs, RXRs, RARs, and T3Rs and their specific ligands regulate the transcription of VD-responsive genes and illustrates the complexity of this interactive network of nuclear receptors.

Animals↗
PubMed1994

The 1,25-dihydroxyvitamin D3 (VD) analogues MC903, EB1089 and KH1060 activate the VD receptor: homodimers show higher ligand sensitivity than heterodimers with retinoid X receptors.

The nuclear receptor for 1,25-dihydroxyvitamin D3 (VD), VDR, belongs to the nuclear receptor superfamily. This ligand-inducible transcription factor mediates the genomic VD signalling pathways by binding to specific response elements in the promoter region of VD regulated genes. Two types of natural VD response elements are used as models for the VDR-mediated transcriptional activation: one is bound by VDR-homodimers and is found in the human osteocalcin gene promoter, and the other is bound by heterodimers of VDR with retinoid X receptors (RXRs) as in the mouse osteopontin promoter. Here, we demonstrate that the VD analogues MC903, EB1089 and KH1060, previously shown to be potent regulators of proliferation and differentiation, are able to act as ligands for VDR and replace VD as a ligand in both nuclear signalling pathways. We found that they have different potency and sensitivity in their ability to stimulate the hormone-dependent promoter element. MC903 and EB1089 provide about 20% higher induction of gene activity than VD in a gene reporter system, whereas KH1060 was more sensitive, inducing transcription at about 100-fold lower doses than VD. Interestingly, VD and its analogues induce VDR homodimer-mediated gene activity at a 3- to 4-fold lower concentration than that of VDR-RXR heterodimers. This suggests that the ligand concentration is an additional regulatory level in the discrimination between signalling pathways involving homo- and heterodimeric hormone receptors.

Animals↗
PubMed1994

Identification and characterization of a vitamin D3 response element of chicken carbonic anhydrase-II.

1,25-Dihydroxyvitamin D3 (VD) controls multiple aspects of homeostasis, cell growth, and differentiation by the action of its nuclear receptor (VDR), which binds to, and activates transcription from, response elements in the promoter region of its target genes. Carbonic anhydrase-II (CA-II), an enzyme important to osteoclast function, has been shown to be regulated by VD. We screened the promoter of chicken CA-II for VDR binding sites and identified a functional VDRE, between positions -1,203 and -1,187. Like the majority of the VDREs described to date, this response element consists of two directly repeated hexameric core binding motifs spaced by three nucleotides and is bound by a heterodimer formed by the VDR and the retinoid X receptor (RXR). We show that the polarity of the binding of this heterodimer is 5'-VDR-RXR-3' in the CA-II VDRE, whereas on a "classical" DR3-type VDRE, such as that of the mouse osteopontin gene, this polarity is reversed to 5'-RXR-VDR-3'. We also show that the polarity of the heterodimeric complex in relation to the basic transcriptional machinery influences the sensitivity of the transcriptional activity to VD. This suggests that the orientation of a hormone response element in its natural promoter context constitutes an additional level of gene regulation.

Animals↗
PubMed1994

Thyroid hormone and retinoic acid receptors form heterodimers with retinoid X receptors on direct repeats, palindromes, and inverted palindromes.

Thyroid hormone [3,5,3'-triiodothyronine (T3)] and retinoic acid (RA) receptors (T3Rs and RARs) are ligand-dependent transcription factors that regulate the transcription of T3- and RA-responsive genes, respectively, by binding to specific DNA sequences as homodimers or as heterodimers with retinoid X receptors (RXRs). These T3 and RA response elements are composed to two copies of the consensus half-site motif PuGGTCA. However, the specificity of the receptor complexes for response elements is dictated by their discrimination of the distance and the relative orientation of the half-sites. We found that both T3R-RXR and RAR-RXR heterodimers act functionally on all three response element configurations: direct repeats, palindromes, and inverted palindromes. On direct repeats, T3R-RXR and RAR-RXR heterodimers showed maximal trans-activation and in vitro DNA binding affinity when the core binding motifs were spaced by 4, 2, or 1 and 5 or 2 nucleotides, respectively, whereas both heterodimer types were mostly active on palindromes with no spacing. The binding of and trans-activation by T3R-RXR and RAR-RXR heterodimers on inverted palindromes was maximal with a half-site spacing of 5 or 6 and 7 or 8 nucleotides, respectively. Inverted palindromes, however, were the most specific response elements, because they were the only ones on which the activities of homodimeric and heterodimeric receptor complexes could be discriminated. We developed a model that suggests a sterical link between the optimal spacings observed with direct repeats and inverted palindromes. Taken together, the experimental data and the model provide further understanding of the regulation of T3-and retinoid-responsive genes.

Animals↗
PubMed1994

cAMP up-regulates IL-4 and IL-5 production from activated CD4+ T cells while decreasing IL-2 release and NF-AT induction.

Seven days after activation with concanavalin A and irradiated spleen cells, murine CD4+ T cells were re-stimulated with ionomycin and phorbol 12-myristate 13-acetate (PMA). IL-2 and IL-4 were determined in the supernatant. When cholera toxin, forskolin together with phosphodiesterase inhibitors or dibutyryl-cAMP were added at the time of re-stimulation, a dose-dependent increase of IL-4 and IL-5 release was noted. IL-2 was down-regulated as reported before. The up-regulation of IL-4 and the down-regulation of IL-2 correlated with an increase of IL-4 mRNA and a decrease of IL-2 mRNA as determined by semi-quantitative reverse transcriptase polymerase chain reaction. Similar results were found with prostaglandin E2 using PMA and ionomycin or plate-bound anti-CD3 antibody as re-stimulants. These results suggest that, in activated CD4+ T cells, cAMP-elevating agents induce a switch of lymphokine production towards a Th2-like phenotype through regulation at the transcriptional level. This is supported by the fact that complex formation between a synthetic nuclear factor of activated T cells (NF-AT) binding site from the IL-2 promoter and nuclear extracts was decreased when cholera toxin was added to re-activated CD4+ T cells, suggesting that cholera toxin and cAMP down-regulate IL-2 expression via decreased NF-AT binding. Finally, since IL-4 has been reported to amplify IL-4 release from activated CD4+ T cells, the autoinduction of IL-4 may very well function via cAMP.

Animals↗
PubMed1994

RZRs, a new family of retinoid-related orphan receptors that function as both monomers and homodimers.

Members of the superfamily of nuclear receptors share the greatest homology in their DNA-binding domains. We have used reverse transcription-polymerase chain reaction and highly degenerate primers based on the amino acid sequence of the zinc finger motif of known nuclear receptors to identify novel members of the family. Starting with rat brain RNA, we have isolated an orphan receptor that we call RZR beta. The sequence of its nearly full-length complementary DNA shows great similarity to RZR alpha, a receptor we recently identified from human umbilical vein endothelial cells. These RZR subtypes represent members of a new family of orphan nuclear receptors that most likely regulate specific gene expression. Sequence comparison with other known nuclear receptors reveals great similarity for both RZR subtypes to retinoic acid and retinoid-X receptors. By Northern blot analyses, we found RZR beta messenger RNA only in brain, whereas RZR alpha is expressed in many tissues. We show here that the RZRs bind as monomers to natural retinoid response elements formed by (A/G)GGTCA half-sites. However, a T-residue in the -1 position of this motif greatly enhances the DNA binding affinity of RZRs, whereas the -2 position has no influence. We show that RZRs can bind as homodimers on response elements formed by palindromes, inverted palindromes, or direct repeats of two TAGGTCA half-sites. Interestingly, these response elements display dramatically reduced affinity for retinoic acid receptor-retinoid-X receptor heterodimers. Thus, the 5'-flanking sequence of hexameric half-sites appears to be crucial to direct the activity of several nuclear receptors. On monomeric as well as dimeric binding sites, RZRs show constitutive transactivational activity that can be enhanced by unidentified components of fetal calf serum.

Amino Acid Sequence↗