Disease relevance of RFXANK

• By pinpointing the interacting residues of the ankyrin repeats of RFXANK, the mechanism of this subtype of severe combined immunodeficiency was revealed [1].
• RFX-B protein expression in human colorectal adenocarcinomas and in normal adjacent tissue was analysed in this study [2].
• The level of CPR-training of the GPs was fairly good: 67% had received BLS training on a manikin and 63% had already attended a cardiac arrest event [3].
• Respondents with significantly higher (more negative reactions) AIDSTRESS scores were: BLS providers, men, paid providers, personnel with more than 3 years of field experience, those working in urban areas, personnel with no formal education beyond high school, and those who stated that their HIV/AIDS training was inadequate [4].
• RESULTS: All persons of the 'only BLS-trained' group delivered the three sequential ('stacked') shocks with the automatic external defibrillator when persistent ventricular fibrillation was simulated [5].

Psychiatry related information on RFXANK

• The effect of basic and advanced cardiac life support (BLS and ACLS) on long-term survival is dependent upon both the response time and the quality of intervention [6].
• When EMS providers at both the BLS and ALS levels leave their training programs, they are armed with newfound knowledge, but they usually lack the appropriate life experiences to excel and survive on the streets [7].

High impact information on RFXANK

• RFXANK restores MHC-II expression in cell lines from patients in group B and is mutated in these patients [8].
• RFX-B is the gene responsible for the most common cause of the bare lymphocyte syndrome, an MHC class II immunodeficiency [9].
• This finding provided the basis for a high-resolution structure-function analysis of the ARD of RFXANK, which allowed us to map the RFX5 interaction domain and residues critical for assembly of the RFX complex [10].
• We discovered that ANKRA2, the closest paralogue of RFXANK, can substitute for RFXANK in the activation of MHC-II genes and that this ability is mediated by its ankyrin repeat domain (ARD) [10].
• We also found that mutations in the fourth ankyrin repeat of RFXANK abolish assembly of the enhanceosome on MHC-II promoters in vivo but not in vitro, suggesting a new role of RFXANK in facilitating promoter occupation in the context of chromatin [10].

Chemical compound and disease context of RFXANK

• All students were assessed and scored on their knowledge and performance of the BLS algorithm (in accordance with the UK Resuscitation Council ('Resuscitation Guidelines for the Citizen') and the use of a trainer defibrillator on a fictional cardiac arrest scenario [11].
• A blood luminescence system (BLS) was employed to analyze blood phagocyte function in response to infusion of endotoxin (4 ng Escherichia coli lipopolysaccharide (LPS)/kg body weight) into 7 healthy human subjects [12].

Biological context of RFXANK

• New functions of the major histocompatibility complex class II-specific transcription factor RFXANK revealed by a high-resolution mutagenesis study [10].
• We investigated the in vivo effects of these mutations and of three other point mutations on the expression of the RFXANK RNA and protein [13].
• A founder effect for this mutation was documented, since all tested patients, except one, display a common haplotype spanning the RFXANK locus [14].
• Additionally, we show that interferon-gamma, which induces Class II MHC gene expression in 293 cells, promotes a shift in the splicing pattern of RFXANK/Tvl-1 toward the transcriptionally active Tvl-L isoform, suggesting that differential splicing of Tvl-1 is a signal-regulated process [15].
• Altogether, we characterize a new type of mutation in the RFXANK gene in a MHC class II-defective patient leading to an uncoordinated expression of the HLA-D genes, and propose that this phenotype is ensured by severely limited amounts of an active, although truncated RFXANK protein [16].

Anatomical context of RFXANK

• The RFXANK vector restored MHCII expression in a T cell line from one patient [17].
• Assignment of ankyrin repeat, family A (RFXANK-like) 2 (ANKRA2) to human chromosome 5q12-->q13 by radiation hybrid mapping and somatic cell hybrid PCR [18].
• Fibroblasts derived from two recently identified bare lymphocyte syndrome patients, EBA and FZA, were found to contain novel mutations in the RFX-B gene [19].
• As the expression of MHC class II correlates with the intensity of the immune response system these results may support the idea that cancer is associated with immunodeficiency and that low levels of RFX-B in interstitial macrophages could partly explain this thesis [2].
• By cell fractionation, ANKRA is found both in the cytosol and associated with membranes enriched in megalin in L2 cells and proximal tubule cells [20].

Associations of RFXANK with chemical compounds

• This indicates that an aromatic ring, but not the phenyl chain of tyrosine, is necessary at position 224 for normal RFXANK function [13].

Physical interactions of RFXANK

• In particular, NFYA and NFYC bound RFXANK/B in vitro [21].
• Ankyrin-repeat family A protein (ANKRA) is a novel protein that interacts directly and specifically with the cytoplasmic tail of megalin in the yeast two-hybrid system and glutathione-S-transferase pull-down assays [20].

Other interactions of RFXANK

• The RFXANK gene encodes one subunit of the heterotrimeric RFX complex that is involved in the assembly of several transcription factors on MHC II promoters [13].
• These genes encode RFXANK, RFXS, RFXAP and CIITA [22].
• Unlike RFX5- and RFXAP-deficient cells, transfection of exogenous class II transactivator (CIITA) into these RFX-B-deficient fibroblasts resulted in the induction of HLA-DR and HLA-DP and, to a lesser extent, HLA-DQ [19].
• Uncoordinated HLA-D gene expression in a RFXANK-defective patient with MHC class II deficiency [16].

Analytical, diagnostic and therapeutic context of RFXANK

• Western blot analysis showed a suppression of nuclear RFX-B protein in the tumour tissue [2].
• Immunohistochemistry revealed that the RFX-B protein levels in macrophages were generally lower in colorectal cancerous tissue compared to adjacent non-cancerous tissue and that focally and not frequently tumour and normal epithelial cells were stained weakly for RFX-B [2].
• By immunofluorescence, ANKRA is concentrated near megalin along the plasma membrane of L2 cells and in the kidney cortex is expressed in glomerular and proximal tubule epithelia which also express megalin [20].
• Many medical schools have required emergency medicine courses for freshmen medical students, usually through participation in BLS (basic life support) or EMT activities [23].
• These results suggest a need to automate and/or prompt the performance of BLS to optimize resuscitation [24].

References