Disease relevance of TBL1XR1

• We have experimentally verified the presence of a previously unknown IRA1/RGS17 fusion in the breast cancer cell line MCF7 [1].
• Thus, this study identified a second community with inherited male pseudohermaphroditism due to 5-alpha-reductase deficiency, confirming the autosomal recessive inheritance of this condition and the generalized abnormality in both C19 and C21 steroid 5-alpha metabolism [2].
• Previous studies led to the isolation of two overlapping cDNA clones that encode polypeptides of TPO (85 residues, C2; 100 residues, C21) recognized by sera from several patients with autoimmune disease that contained antimicrosomal autoantibodies [3].
• In contrast with Clostridium limosum exoenzyme, component C21 of the Clostridium botulinum C2 toxin, which ADP-ribosylates G-actin, depolymerized basal F-actin and inhibited N-formyl-peptide-induced actin polymerization in electropermeabilized HL60 cells [4].
• Serum concentrations of 17OH-progesterone were studied serially over 24 hours in 13 treated and untreated patients with the C21 hydroxylase form of congenital adrenal hyperplasia [5].

Psychiatry related information on TBL1XR1

• The e6G4-C21 base pair has a configuration similar to a normal Watson-Crick base pair, except with one three-centered hydrogen bond pair and one direct hydrogen bond between e6G4 and C21 [6].

High impact information on TBL1XR1

• Although SMRT derepression corresponds with the recruitment of TBL1/TBLR1, this complex alone is insufficient to relieve repression [7].
• Certain C19 and C21 steroid metabolites, when incubated with normal human bone marrow cells in culture, increased the number of erythroid colonies in the presence of erythropoietin [8].
• By using specific small interference RNAs (siRNAs), we demonstrate that HDAC3 is essential, whereas TBL1 and TBLR1 are functionally redundant but essential for repression by unliganded thyroid hormone receptor [9].
• The e6G4-C21 base pair has a configuration similar to a normal Watson-Crick base pair, except with bifurcated hydrogen bonds between e6G4 and C21, and the ethyl group is in the proximal orientation [10].
• The fusion gene encodes the full-length RGS17 protein, a regulator of G protein-coupled signaling, under the control of the IRA1 gene promoter [1].

Chemical compound and disease context of TBL1XR1

• Phospholipids and a novel glycine-containing lipoamino acid in Cytophaga johnsonae Stanier strain C21 [11].
• The procedure utilizes a strain of Escherichia coli that becomes resistant to bacteriophage C21 in the presence of galactose [12].

Biological context of TBL1XR1

• Recently, it has been shown that TBLR1, another homologue whose gene resides on chromosome 3, and TBL1X act as a corepressor/coactivator exchanger for several nuclear receptors and transcription factors [13].
• We specifically propose that residues C75, U20 and C21 form the basis of the catalytic region and are close to the cleavable phosphate [14].
• We studied C19 and C21 urinary steroid metabolites, 5 alpha/5 beta and 11 oxo/11 hydroxy metabolite pairs as well as the ratios of the total 5 alpha/total 5 beta and total 11 oxo/total 11 hydroxy metabolites in 24-h urine samples from 17 prepubertal Hispanic girls with premature adrenarche and seven controls [15].
• Despite the widespread use of the C21 progestin medroxyprogesterone acetate (MPA) in hormone replacement therapy and gynecological practice, its effects on bone density are uncertain, with contradictory reports in the literature [16].
• Interrelationships of circulating maternal steroid concentrations in third trimester pregnancies. I. C21 steroids: progesterone, 16 alpha-hydroxyprogesterone, 17 alpha-hydroxyprogesterone, 20 alpha-dihydroprogesterone, delta 5-pregnenolone, delta 5-pregnenolone sulfate, and 17-hydroxy delta 5-pregnenolone [17].

Anatomical context of TBL1XR1

• Here, we used the frog oocyte system to demonstrate that unliganded TR interacts with TBLR1 and recruits TBLR1 to its chromatinized target promoter in vivo, accompanied by histone deacetylation and gene repression [18].
• In contrast, the metabolizable C19 and C21 steroids, 5 alpha-dihydrotestosterone and 20 alpha-dihydroprogesterone, which inhibited the conversion of E1 to E2 by microsomes, stimulated E2 formation from E1 by villi [19].
• The control follicles incubated at 1500 h produced steroids in nanogram amounts and the granulosa cells in vitro now produced C21 steroids, especially P4 [20].
• MATERIAL AND METHODS: The effect of medroxyprogesterone acetate (MPA) and norethisterone (NET), which represent the two different classes of C21- and C19-progestogens, respectively, was investigated on proliferation of smooth muscle cells from human coronary artery in vitro [21].
• This suggests that the atrophic testes of these animals may have a limited capacity to produce biologically significant amounts of androgens from C21 steroids [22].

Associations of TBL1XR1 with chemical compounds

• Cytochrome p450c17 (CYP17) converts the C21 steroids pregnenolone and progesterone to the C19 androgen precursors dehydroepiandrosterone (DHEA) and androstenedione, respectively, via sequential 17alpha-hydroxylase and 17,20-lyase reactions [23].
• The chiral phosphono acetate method was used for the highly stereoselective attachment of the alpha-side chain to the bicyclic C6-C21 intermediate carrying a carbonyl group at C6 [24].
• Searches for natural ligands have revealed that the PXRs are activated by C21 steroids, including pregnenolone and progesterone, suggesting that these orphan receptors define a novel steroid hormone signaling pathway [25].
• Recombinant mutant type II 3 beta HSD enzyme carrying the Y254D substitution exhibits no detectable activity with C21 delta 5-steroid pregnenolone or C19 delta 5-steroid dehydroepiandrosterone used as substrate [26].
• These metabolites are not the products of the enzyme reaction catalyzed by the cytochrome P450 steroid 6 alpha-hydroxylase of human liver (and other tissues), which affects the 6 alpha-hydroxylation of C19- and C21-delta 4-3-ketosteroids (e.g., progesterone, testosterone, and cortisol), but does not act upon 5 alpha-reduced steroids [27].

Other interactions of TBL1XR1

• TBLR1 co-precipitates with SMRT, a co-repressor of nuclear hormone receptors, and co-precipitates in complexes immunoprecipitated by antiserum to HDAC3 [28].

Analytical, diagnostic and therapeutic context of TBL1XR1

• Using chromatin immunoprecipitation, we demonstrate that both oncoproteins recruit TBLR1, as well as N-CoR, to its target promoter, leading to histone deacetylation and transcriptional repression [29].
• The urinary 5 beta/5 alpha ring A-reduced metabolites of C19 and C21 steroids from obligate carrier parents of male pseudohermaphrodites with 5 alpha-reductase deficiency were analyzed by gas chromatography [30].
• The steroidogenic characteristics of primary testicular cell cultures from adult hypophysectomized rats: enhanced formation of C21 steroids [31].
• Correlation between binding affinities of C21 steroids for the maturation-inducing steroid membrane receptor in spotted seatrout ovaries and their agonist and antagonist activities in an oocyte maturation bioassay [32].
• One such antiserum was studied in detail; cross-reactivity with other C21 steroids normally present in human plasma was negligible and it proved possible to establish a radioimmunoassay which satisfied all criteria of reliability [33].

References