Disease relevance of Eif4g2

• Their outgrowth in immunocompetent syngeneic mice was shown to inversely correlate with p97 antigen expression, and lines that express higher p97 levels elicited a stronger delayed-type hypersensitivity response when injected into the footpads of mice immune to p97 [1].
• Mice immunized with v-p97NY rejected transplants of syngeneic mouse melanoma expressing p97 [2].
• The L49 monoclonal antibody against the p97 antigen on melanomas and carcinomas was chemically conjugated to E. coli beta-galactosidase (beta-gal), forming a largely monomeric conjugate with preserved enzymatic activity [3].

High impact information on Eif4g2

• Cryoelectron microscopy and single-particle analysis revealed that a major conformational change of p97 during the ATPase cycle occurred upon nucleotide binding and not during hydrolysis as previously hypothesized [4].
• Essential role of NAT1/p97/DAP5 in embryonic differentiation and the retinoic acid pathway [5].
• Binding of the p47 complex directs p97 to act in the post-mitotic fusion of Golgi membranes [6].
• In rat liver cytosol, Ufd1 and Npl4 form a binary complex, which exists either alone or bound to p97 [6].
• Because p97 is known to bind to the endoplasmic reticulum membrane protein AMFR (gp78), an E3 ligase, we propose a model in which p97, mPNGase, and mHR23B mediate interaction of the endoplasmic reticulum with the proteasome [7].

Biological context of Eif4g2

• The Eif4g2 polypeptide contains multiple potential N-linked glycosylation sites as well as protein kinase C and casein kinase II phosphorylation sites [8].
• The 3810-nucleotide Eif4g2 cDNA contains a 907-amino-acid open reading frame that codes for a polypeptide with a predicted molecular mass of 102 kDa [8].
• Southern blot analysis of DNA from interspecific backcross mice shows that Eif4g2 is localized to distal mouse chromosome 7 in a region syntenic with human chromosome 11p15 [8].
• Surprisingly, the protein associates with the cytoplasmic side of various intracellular membranes, accumulates prior to mitosis, and copurifies with the cdc48 homolog p97/valosin-containing protein [9].
• This suggests that nuclear import of protein kinase C alpha is independent of p97/importin/karyopherin beta and independent of GTP [10].

Anatomical context of Eif4g2

• We activated T-lymphocytes in vivo with SEB, expanded them in vitro with IL-2, and directed them against a tumour target with the BAb 500A2 x 96.5, specific for the murine CD3 antigen and the melanoma p97 antigen expressed by the CL62 tumour [11].

Associations of Eif4g2 with chemical compounds

• Because Ang II increased tyrosine phosphorylation of only the 97-kD protein, we characterized p97 further [12].

Analytical, diagnostic and therapeutic context of Eif4g2

• Northern blot analysis shows that Eif4g2 is ubiquitously expressed at high levels in all human and mouse tissues examined [8].
• Nat1- and Nat2-specific mRNA, determined by quantitative real-time polymerase chain reaction, was detected in all tissues examined and did not differ significantly (p > 0.05) between Nat2 KO and WT mice [13].
• Western blot analysis of whole cell lysates using anti-phosphotyrosine antibody revealed that GH promotes the tyrosyl phosphorylation of a 121-kDa protein and several other proteins (p97, p42, p39) in a dose- and time-dependent fashion [14].
• We can show that, in contrast to the nuclear localization signal-dependent transport, the phorbol ester-induced transport of protein kinase C alpha is not affected by microinjection of antibodies against the nuclear import factor p97/importin/karyopherin beta or microinjection of non-hydrolyzable GTP-analogs [10].

References