Disease relevance of EIF4G2

• The transcripts of SFRP1,CEP63 and EIF4G2 genes are frequently downregulated in transitional cell carcinomas of the bladder [1].
• Efficient cleavage of both forms of eukaryotic initiation factor 4G (eIF4G-1 and eIF4G-2) has been achieved in HeLa cells by incubation with hybrid proteins containing poliovirus 2Apro [2].
• DAP-5 is involved in MycN/IFNgamma-induced apoptosis in human neuroblastoma cells [3].
• p97 is a 97,000 molecular weight cell-surface glycoprotein, which is present in human melanomas but in only trace amounts in normal adult tissues [4].
• Immunization with v-p97NY could induce humoral and cell-mediated immunity to p97, including delayed-type hypersensitivity, in mice and in two of two monkeys (Macaca fascicularis) [5].

Psychiatry related information on EIF4G2

• On whole body images, the anti-Fab HMWA appears to be more tumor selective than Fab preparations that target the p97 antigen for melanoma, and there is less uptake in liver [6].

High impact information on EIF4G2

• Our strategy was to characterize interspecies somatic cell hybrids derived from human fibroblasts or lymphocytes for expression of p97 and presence of human chromosomes [4].
• Of 14 hybrids, 6 contained chromosome 3 and expressed p97, and 8 were negative for both [4].
• Amino acid sequence and iron binding studies have shown that p97 is structurally and functionally related to transferrin [4].
• In an in vitro model of retrotranslocation, the AAA ATPase p97, an enzyme critical for ERAD, was the only cytosolic cofactor required for protein export from isolated phagosomes [7].
• We also report that p97 binds eIF2beta through its C-terminal domain and localizes to ribosome through its N-terminal MIF4G domain [8].

Chemical compound and disease context of EIF4G2

• By employing a functional approach we examined the role of DAP-5 in human neuroblastoma cells that are sensitized for IFNgamma-induced apoptosis by tetracycline controlled MYCN expression [3].
• These lymphocytes immunized in culture were used to produce human-human or human-mouse hybridomas secreting monoclonal antibodies specific for digoxin, hemocyanin, a recombinant fragment of the gp120 envelope glycoprotein of human immunodeficiency virus (PB1), or a melanoma-associated antigen (p97) [9].
• We now show that the ability of v-p97NY to induce delayed-type hypersensitivity to p97 improved if the vaccinated mice were given cyclophosphamide (Cy) on the day of vaccination [10].

Biological context of EIF4G2

• In addition, downregulation of both CEP63 and EIF4G2 gene transcription was associated with invasive tumors [1].
• While cap-dependent translation from this transfected vector was reduced during Fas-induced apoptosis, the translation via the DAP5 IRES was selectively maintained [11].
• An internal ribosome entry site (IRES) element capable of directing the translation of a reporter gene when subcloned into a bicistronic vector was identified in the 5' untranslated region of DAP5 mRNA [11].
• Transient transfection experiments show that p97 suppresses both cap-dependent and independent translation, while eIF4G supports both translation pathways [12].
• The rescued DAP-5 cDNA fragment which conveyed resistance to IFN-gamma-induced cell death was expressed from the vector in the sense orientation [13].

Anatomical context of EIF4G2

• The activity of NAT1 showed significant variance from leukocytes with different genotypes [14].
• Although each cell line expressed the proto-oncogene product Fes, antisera specific for Fes did not recognize p97 in immunoblotting experiments [15].
• Characterization of the T cell clones demonstrated the presence of both I-Ak and I-Ek-restricted clones, although the majority of clones recognized p97 in the context of I-Ek [16].
• We have mapped the binding domains on p97 for the NLS receptor and the nuclear pore [17].
• Tumor-infiltrating lymphocytes (TIL) were obtained from a mouse melanoma cell line (CL 62) transfected with the gene for the human melanoma Ag p97 [18].

Associations of EIF4G2 with chemical compounds

• This study reveals why human NAT1 acetylates the sunscreen additive p-aminobenzoic acid and tobacco smoke carcinogen 4-aminobiphenyl, but not o-toluidine and other arylamines linked to bladder cancer [19].
• We propose a model that assigns the cytosolic face of the ER as a midpoint to which luminal ERAD substrates emerge and p97/Cdc48p and the proteasome are recruited [20].
• Site-directed mutagenesis of conserved cysteine residues in the pore- and receptor-binding domains identified two cysteines, C223 and C228, that were required for p97 to bind the nuclear pore [17].
• In a permeabilized cell protein import assay, a mutant p97 with alanine substituted for Cys-158 is unable to support import in the presence of NLS receptor and Ran [21].
• The N-ethylmaleimide sensitivity of the p97 for docking was investigated and found to be due to inhibition of p97 binding to the pore complex and to the NLS receptor [17].

Regulatory relationships of EIF4G2

• Death associated protein-5 (DAP-5) is a ubiquitously expressed member of the translation initiation factor eIF4G family that lacks the eIF4E binding site [3].

Other interactions of EIF4G2

• The N-terminal part of DAP-5 has 39% identity and 63% similarity to the central region of mammalian p220 [13].
• Intriguingly, it comprised part of the coding region which corresponds to the less conserved C-terminal part of DAP-5 and directed the synthesis of a 28-kDa miniprotein [13].
• DAP-5, a novel homolog of eukaryotic translation initiation factor 4G isolated as a putative modulator of gamma interferon-induced programmed cell death [13].
• When the HeLa cell extract was supplemented with a combination of eIF2, eIF2B, and p97, the capacity to synthesize a protein from an uncapped mRNA became comparable to that from the capped counterpart stimulated with a combination of eIF2, eIF2B, and eIF4E [22].
• In humans, two isoforms have been characterized that are generated by alternative splicing and contain either exon 1a or 1b (hAAG1 or hAAG2) [23].

Analytical, diagnostic and therapeutic context of EIF4G2

• Among the differentially expressed genes, SFRP1,CEP63 and EIF4G2 were further validated by quantitative RT-PCR in a series of 50 transitional cell carcinomas [1].
• METHODS: Peripheral blood from 140Han people were collected and analyzed for NAT1 genotypes by allele-specific PCR combining with PCR-based restriction fragment length polymorphism-based procedure [14].
• The NAT1 phenotype were determined according to the NAT1 enzyme kinetics in leukocytes by HPLC method and the values of intrinsic clearance (Cl(int)) and V(max) and Michaelis constant (K(m)) of NAT1 were calculated [14].
• Although fibroblasts and lymphocytes express only small amounts of p97, we were able to type the hybrids for p97 by using monoclonal antibodies in highly sensitive and specific immunoassays [4].
• Localization of 131I-labeled p97-specific Fab fragments in human melanoma as a basis for radiotherapy [24].

References