Disease relevance of NR1D2

• Cardiac ischemia (RR= 1.8; 95% CI=1.0 to 3.4) and an increased RVR (RR=1.7; 95% CI=0.9 to 3.4) tended to increase the risk of weaning failure [1].
• Unilateral renal injury, whether caused by ureteral obstruction or ischemia, is followed by an increase in RVR, a decrease in RBF, and eventual tubular atrophy [2].

High impact information on NR1D2

• Peripheral alpha antagonists not only preserve renal hemodynamics, but decrease RVR and maintain renal perfusion autoregulation in the face of decreased systemic perfusion pressures [3].
• ROR alpha1 and RVR are orphan members of the superfamily of nuclear hormone receptors which constitutively activate and repress, respectively, gene transcription by binding to a common DNA sequence [4].
• Moreover, Northern blot analysis demonstrated a direct modulation of an exogenously introduced N-myc gene by ROR alpha1 and RVR in COS-1 cells [4].
• Yet for each picomolar increment in plasma ANP during immersion, the corresponding increases in urinary excretion of cyclic guanosine monophosphate (26 vs. 279 pmol/min) and sodium (9 vs. 47 mumol/min) and the reciprocal lowering of RVR (0.7 vs. 1.9 U) were blunted in the diabetic versus control group [5].
• With liberal sodium, no differences in blood pressure were detected, whereas angiotensin I induced a higher response of ERPF ( DD 40+/-5% vs II 35+/-4%, p<0.05) and RVR ( DD 105+/-20% and II 89+/-16% p<0.05) in DD-homozygotes [6].

Biological context of NR1D2

• This investigation utilised the mammalian two hybrid system and transfection analysis to demonstrate that Rev-erbA alpha and RVR will not efficiently interact with either ID-I or ID-II separately from RIP13a or RIP13delta1 [7].
• Like Rev-Erb, BD73 binds as a monomer to a DNA sequence which consists of a specific A/T-rich sequence upstream of the consensus hexameric half-site specified by the P box of the DNA-binding domain [8].
• Under the conditions examined, neither BD73 nor Rev-Erb activated reporters containing multiple copies of their common binding site [8].
• Amino acid sequence comparisons suggest that the A box sequence, which has been suggested to mediate monomer binding by other superfamily members, lies closer to the DNA-binding domain in BD73 and Rev-Erb than in other receptors [8].
• Unlike Rev-Erb, in which the opposite strand of the C-terminal coding region encodes the C-terminal portion of a variant thyroid hormone receptor isoform, the opposite strand of the C-terminal coding region of BD73 does not have any extensive open reading frames [8].

Anatomical context of NR1D2

• BD73 messenger RNA is expressed in a wide variety of tissues and cell lines [8].
• During embryonic development, we noticed a striking specific distribution of Rev-erb beta transcripts in the notochord at 24 h and later on, in the floor plate of the neural tube [9].
• The role of radiology in screening and diagnosis is discussed with special attention to renal vein sampling for renin assay (RVR) and digital subtraction angiography (DSA) [10].

Associations of NR1D2 with chemical compounds

• The phenylalanine residues, F402 and F441, in RVR and Rev-erbA alpha, respectively, were critical residues in supporting corepressor interaction [11].
• RVR/Rev-erb beta/BD73 is an orphan steroid receptor that has no known ligand in the "classical' sense [12].
• The Rev-erb beta gene product does not interact with retinoid X receptors, as revealed by gel shift experiments [9].
• Rev-erb beta binds to DNA as a monomer and recognizes the same binding motif as the alpha gene product [9].
• Uric acid excretion rate rose remarkably after nifedipine and the magnitude of the changes seemed intimately related to the basal level of RVR [13].

Other interactions of NR1D2

• Rev-erbA alpha and RVR are orphan nuclear receptors that function as dominant transcriptional silencers [11].
• Two receptor interaction domains in the corepressor, N-CoR/RIP13, are required for an efficient interaction with Rev-erbA alpha and RVR: physical association is dependent on the E region of the orphan receptors [7].
• In conclusion, our study has identified a new corepressor interaction region, CIR-1, in the N terminus of helix 3 in the E region of RVR and Rev-erbA alpha, that is required for transcriptional silencing [11].
• RV14 upregulated the expression of the mRNA and protein of intercellular adhesion molecule-1 (ICAM-1), the major RV receptor, and it increased the cytokine production [14].
• The results obtained point to the involvement of a carboxyl-terminal sequence adjacent to the second zinc finger of the Rev-erb beta DBD in protein-DNA interaction as a monomer or in protein-DNA and protein-protein interactions as a homodimer [15].

Analytical, diagnostic and therapeutic context of NR1D2

• In situ hybridization experiments show that Rev-erb beta is expressed in the central and peripheric nervous system, spleen, and mandibular and maxillar processes, as well as in blood islands [9].
• CONCLUSIONS: The RVR is more accurate than other commonly utilized clinical tools in predicting the outcome of weaning from mechanical ventilation [16].
• Only insignificant increments of glomerular filtration (RVR) was markedly reduced (P less than 0.001) [13].
• DNA bending assays, high-resolution footprinting, molecular modeling, and site-directed mutagenesis were used to analyze the structural features of the interaction between the DNA-binding domain (DBD) of the nuclear receptor Rev-erb beta and its DNA target sites [15].
• In cyclosporine-treated renal allograft hypertensives, amlodipine and perindopril lower blood pressure equally and reduce RVR to the same extent [17].

References