Disease relevance of EIF4H

• Herpes simplex virus virion host shutoff protein is stimulated by translation initiation factors eIF4B and eIF4H [1].
• Fluorescent in situ hybridization (FISH) analyses demonstrated a deletion of the elastin gene in the Williams syndrome critical region (WSCR) [2].

High impact information on EIF4H

• Also examined is the influence of ancillary protein factors (eIF4B, eIF4G, and eIF4H) on this activity [3].
• The combinations of eIF4A, eIF4A + eIF4B, eIF4A + eIF4H, and eIF4F showed differences in their ability to unwind chemically modified duplexes [4].
• Functional studies have revealed that recombinant heIF4H functions identically to rabbit eIF4H in stimulating protein synthesis, and the ATP hydrolysis and helicase activities of eIF4A [5].
• Recombinant human eIF4H (heIF4H) was purified to greater than 95% homogeneity and shown to have similar physical characteristics to eIF4H purified from rabbit reticulocyte lysate as described previously [5].
• Three tryptic fragments of eIF4H yielded amino acid sequences that were 100% identical to a human sequence found in the GeneBankTM that codes for a previously uncharacterized protein (HUMORFU_1) [6].

Biological context of EIF4H

• In one patient with uncomplicated disease, HBV DNA was integrated into host chromosome 7 q11.23 in the WBSCR1 gene [7].
• mRNA decay during herpes simplex virus (HSV) infections: protein-protein interactions involving the HSV virion host shutoff protein and translation factors eIF4H and eIF4A [8].
• Vhs interacts with the cellular translation initiation factor eIF4H, and several point mutations that abolish its mRNA degradative activity also abrogate its ability to bind eIF4H [8].
• Further mapping by loss of heterozygosity analysis both by microsatellite marker and SNP profiling demonstrated a 1.5 Mb deletion beyond the telomeric end of the typical WSCR [2].

Associations of EIF4H with chemical compounds

• The calculated molecular weight of the protein encoded by this sequence, its predicted cyanogen bromide fragmentation, and calculated isoelectric point are all consistent with those determined experimentally for eIF4H [6].
• This interaction was verified by glutathione S-transferase pull-down experiments and by coimmunoprecipitation of Vhs and epitope-tagged eIF4H from extracts of mammalian cells [9].

Other interactions of EIF4H

• LIMK1 and WSCR1 may be particularly relevant when explaining cognitive defects observed in WS patients [10].
• Within this region we have completely characterized 200 kb containing the genes LIMK1, WBSCR1, and RFC2 [11].
• Activity was strongly enhanced by the addition of RRL, eIF4H, or the related translation factor eIF4B [1].
• Previous work has shown that vhs forms a complex with translation initiation factor eIF4H, which displays detectable RNase activity in the absence of other viral or host proteins [1].
• Interestingly, only isoform 1 of two transcript variants of eukaryotic translation initiation factor 4H was greatly up-regulated in most of the tumor tissues [12].

Analytical, diagnostic and therapeutic context of EIF4H

• Secondary structure analysis of heIF4H by circular dichroism suggest that eIF4H has a mostly beta-sheet structure, which appears similar to other RNA recognition motif-containing proteins [5].
• Northern blot analysis shows that eIF4H is expressed ubiquitously in human tissues, and displays different levels of expression in given tissues relative to eIF4B [5].
• Site-directed mutagenesis of Vhs and eIF4H revealed residues of each that are important for their mutual interaction, but not for their interaction with eIF4A [8].
• They include eukaryotic translation initiation factor 4H, inorganic pyrophosphatase, anterior gradient 2 homologue, aldolase A, and chloride intracellular channel 1, whose elevated expression in tumor tissues was confirmed by Western blot analysis and immunohistochemistry [12].
• Three signals were detected using the Oncor fluorescent in situ hybridization probe for elastin-Williams syndrome (WSCR) suggesting that the break in chromosome 7 is within the elastin-Williams gene [13].

References