Disease relevance of NKRF

• In unstimulated cells, however, NRF inhibits HIV-1 LTR activity at the level of transcription elongation [1].
• NF-kappaB-repressing factor inhibits elongation of human immunodeficiency virus type 1 transcription by DRB sensitivity-inducing factor [1].
• Ten subjects had normal renal function (NRF; creatinine clearance [CLCR] > or = 85 ml/min/1.73 m2), six subjects had mild to moderate renal insufficiency (MMRI; CLCR between 25 and 73 ml/min/1.73 m2), and 10 subjects had severe renal insufficiency (SRI; CLCR < or = 10 ml/min/1.73 m2) [2].
• METHODS: The study included patients with CHC and ESRD (n = 91) or normal renal function (NRF, n = 159) [3].
• Compared to patients with NRF and stage III-IV fibrosis, those with ESRD and stage III-IV fibrosis had a significantly higher frequency of a history of DM (OR = 8.014, p= 0.0031) and lower frequency of elevated AST (OR = 0.054, p= 0.004), which were independent of the frequencies of lower levels of ALT and albumin, and AST/ALT ratio >1 [3].

High impact information on NKRF

• Constitutive silencing of IFN-beta promoter is mediated by NRF (NF-kappaB-repressing factor), a nuclear inhibitor of NF-kappaB [4].
• Here, we describe the identification and functional characterization of the NRE-binding protein, called NRF (NF-kappaB-repressing factor), which abolishes the transcriptional activity of the bordering NF-kappaB- binding sites by a distance-independent mechanism [4].
• Our data strongly suggest that the NRF-mediated inhibition of NF-kappaB is a critical component of the IFN-beta gene silencing prior to viral infection [4].
• Decreased PGC1 expression may be responsible for decreased expression of NRF-dependent genes, leading to the metabolic disturbances characteristic of insulin resistance and DM [5].
• Mutation of the -6.7-kb NRE site in the hiNOS promoter resulted in loss of NRF binding and increased basal but not cytokine-stimulated hiNOS transcription in promoter transfection experiments [6].

Biological context of NKRF

• Identification of a negative response element in the human inducible nitric-oxide synthase (hiNOS) promoter: The role of NF-kappa B-repressing factor (NRF) in basal repression of the hiNOS gene [6].
• Our data show that the endogenous NRF is required for transcriptional activation of the HIV-1 LTR in stimulated cells [1].
• During large-scale sequencing of a human fetal brain cDNA library we isolated a novel human cDNA that proved to be a correct full-length NRF cDNA [7].
• Full-length NRF cDNA is 3247 bp long, contains three exons and maps to human chromosome Xq24 [7].
• The NRF 5'UTR also functions as a translational enhancer in the context of monocistronic mRNAs [8].

Anatomical context of NKRF

• In fibroblasts, the expression of the NRF antisense RNA releases the endogenous IFN-beta gene transcription [4].
• Translation of NRF mRNA is mediated by highly efficient internal ribosome entry [8].
• The molecular weight of the serum neurite retraction factor (NRF) has been demonstrated to be approximately 70 x 10(3) by gel permeation on LKB-Ultrogel AcA-44 [9].
• NRF is present in sera of various species studied, including human, cattle, sheep, rabbit and horse, but not in tissue extracts of kidney, heart, lung skeletal muscle, and brain of the rat [9].
• Data showed that a protein factor from nuclear extracts of K562 cells specifically interacted with NRF DNA fragment [10].

Associations of NKRF with chemical compounds

• Since treatment with actinomycin D releases NRF from nucleoli the identified RNA binding motifs might act as nucleolar localization signals [11].
• Binding of NRF to the LTR in unstimulated cells prevents recruitment of elongation factor DRB sensitivity-inducing factor and formation of processive elongation complexes by hyperphosphorylated RNA polymerase II [1].
• From this study, it is concluded that the major metabolite of the cancer chemopreventive oltipraz is a phase 2 enzyme inducer of comparable potency that activates the ARE and initiates nuclear translocation of transcription factor Nrf 2 [12].
• NRF remained unchanged with Respir+, whereas it significantly decreased with Nozovent and Pernazène (p<0.0001) [13].
• Strength training leading to RF resulted in reductions in resting concentrations of IGF-1 and elevations in IGFBP-3, whereas NRF resulted in reduced resting cortisol concentrations and an elevation in resting serum total testosterone concentration [14].

Physical interactions of NKRF

• Here we show that an NF-kappaB-repressing factor (NRF) binds to the IL-8 promoter NF-kappaB-NRE [15].

Regulatory relationships of NKRF

• The NF-kappa b repressing factor is involved in basal repression and interleukin (IL)-1-induced activation of IL-8 transcription by binding to a conserved NF-kappa b-flanking sequence element [15].

Analytical, diagnostic and therapeutic context of NKRF

• In A549 and HeLa human cells, constitutive NRF mRNA expression is detected by RT-PCR [6].
• The other two, ZNF183 and ITBA4, were novel genes whose function cannot directly be inferred from their sequence analysis [16].
• Treatment with phase II inducers leads to increased accumulation of nuclear factor-erythroid 2 p45-related factor (NRF) 2 in the nucleus, which was associated with increased binding to this ARE as determined by electrophoretic mobility shift assay [17].
• CONCLUSION: Dose adjustment will need to be made on the basis of titration to the desired clinical response and tolerability in patients with SRI just as in subjects with NRF [2].
• In order to calculate accurately the NRF for prostatic carcinoma, the histologic section must have been reviewed by a pathologist and 150 nuclei traced after random selection [18].

References