Disease relevance of ABCE1

• CTL precursors reactive to these 2 ABCE1 peptides were detected in the peripheral blood mononuclear cells (PBMCs) of the colon cancer patient, from whom the TILs had been obtained [1].
• Moreover, cells expressing a low level of RLI (VAS3 and VAS 4) are partially resistant to EMCV infection [2].
• The overexpression of RLI in stably transfected HeLa cells inhibits the antiviral activity of IFN on encephalomyocarditis virus but not on vesicular stomatitis virus [3].
• The overexpression of RLI causes a decrease in RNase L activity and a twofold enhancement of HIV production [4].
• We show here that RLI increases during the course of human immunodeficiency virus type 1 (HIV-1) infection, which may be related to the downregulation of RNase L activity that has been described to occur in HIV-infected cells [4].

High impact information on ABCE1

• Here we identify such a protein (HP68), described previously as an RNase L inhibitor, and demonstrate that it associates post-translationally with HIV-1 Gag in a cell-free system and human T cells infected with HIV-1 [5].
• Germline alterations of the RNASEL gene, a candidate HPC1 gene at 1q25, in patients and families with prostate cancer [6].
• In contrast, cells expressing siRNA to the RNase L inhibitor RLI (HP68) showed enhanced apoptosis in response to Topo I inhibitor alone or in combination with TRAIL [7].
• In conclusion, hepatic overexpression of PKR and reduced expression of RNase L inhibitor seem to contribute to the anti-HCV mechanism characteristically [8].
• Intrahepatic mRNA expression of interferon-inducible antiviral genes in liver diseases: dsRNA-dependent protein kinase overexpression and RNase L inhibitor suppression in chronic hepatitis C [8].

Biological context of ABCE1

• We identified a gene coding a member of the ATP-binding cassette transporter (ABCE1), which is known as an inhibitor to the 2-5A/RNase L system, a central pathway of interferon action, and its gene expression is amplified in drug-resistant cells [1].
• The RLI gene was localized to locus 4q31 by in situ hybridization indicating that this gene and other enzymes of the 2-5A pathway are not organized in cluster in the human genome [9].
• RNase L inhibitor (RLI) antisense constructions block partially the down regulation of the 2-5A/RNase L pathway in encephalomyocarditis-virus-(EMCV)-infected cells [2].
• Translation is a highly regulated process important to development and pathologies such as cancer, making ABCE1 a potential target for therapeutics [10].
• The human ABCE1 gene contains 16 introns, and the extremely high degree of amino acid identity allows the evolution of its introns to be examined throughout eukaryotes [10].

Anatomical context of ABCE1

• No definite cytotoxicity was observed against normal T cell blasts, irrespective of the expression of the ABCE1 mRNA [1].
• The ABCE1 mRNA was ubiquitously expressed in tumor cell lines, as well as normal cells or tissues [1].
• ABCE1, a member of ATP-binding cassette transporter gene, encodes peptides capable of inducing HLA-A2-restricted and tumor-reactive cytotoxic T lymphocytes in colon cancer patients [1].
• Since RNase L had been shown to be down regulated upon encephalomyocarditis (EMCV) infection, we stably transfected HeLa cells with a RLI antisense cDNA expressing vector [2].
• We found that a fraction of cellular RNase L and RLI is localized in the mitochondria [11].

Associations of ABCE1 with chemical compounds

• Intramolecular amidofuran cycloadditions across an indole pi-bond: an efficient approach to the aspidosperma and strychnos ABCE core [12].
• Lysine labeling with NHS-biotin and cross-linking with DTSSP revealed that the 35 amino acid RLI motif at the N terminus is solvent exposed [13].
• Mutagenesis of the cysteine at position 6 yielded a functional ABCE1 with the ferredoxin-like Fe-S cluster in a paramagnetic [3Fe-4S](+) state [14].

Physical interactions of ABCE1

• Likewise RLI is coimmunoprecipitated with the RNase L complex by a nuclease-specific antibody [3].

Other interactions of ABCE1

• We have recently cloned a cDNA coding for RLI, a RNase-L-specific protein inhibitor [2].
• In this manuscript, sequence analysis has been employed to analyse two families of twin-NBD proteins, ABCE and ABCF [15].
• X-ray structure of RLI, an essential twin cassette ABC ATPase involved in ribosome biogenesis and HIV capsid assembly [16].
• In the present study, we investigated the levels of 2-5A synthetase, RNase L and RLI in patients with CFIDS as compared to healthy controls [17].
• Seven clones were found to be underexpressed; three of the clones showed significant similarity with sequences of the human genes encoding RNase L inhibitor, human tissue factor and ARCN1 (archain vesicle transport protein 1), a highly conserved species which is related to vesicle structure and trafficking proteins [18].

Analytical, diagnostic and therapeutic context of ABCE1

• These results indicate that the ABCE1 and its peptides could be target molecules in specific immunotherapy for HLA-A2(+) colon cancer patients [1].
• In contrast, reduction of RLI levels in RLI antisense cDNA-expressing clones reverses the inhibition of RNase L activity associated with HIV multiplication and leads to a threefold decrease in the viral load [4].
• Quantitative Competitive PCR (Q/C PCR) analysis showed a statistically significant decrease in RLI mRNA present in the peripheral blood lymphocytes (PBL) of patients with CFIDS (n = 25, mean = 569, S.E = 154) as compared to RLI mRNA level present in peripheral blood lymphocytes (PBL) of healthy controls (n = 15, mean = 2296, S.E = 506; p < 0.0001) [17].
• Quantitative RT-PCR measurements of RNA from different PBL cell types separated by fluorescence activated cell sorting (FACS) showed that complete RNASEL mRNA levels were significantly elevated in granulocytes compared with all other PBL cell types, whereas expression was lowest in CD8(+) T cells [19].
• Esophageal pressure amplitude (DeltaPes), inspiratory pulmonary resistance (RLI) and inspiratory flow limitation score (FS) are used as indices of upper airway obstruction for the titration of nasal continuous positive airway pressure (nCPAP) in patients with obstructive sleep apnea syndrome (OSAS) [20].

References