Disease relevance of EIF3S6IPP2

• Amplification and overexpression of p40 subunit of eukaryotic translation initiation factor 3 in breast and prostate cancer [1].
• We previously identified a 170-kDa protein (p170) highly expressed in lung cancers as the major subunit of the eukaryotic translation initiation factor 3 (eIF3). p170 was recently cloned and little is known concerning its characteristics and subcellular localization [2].

High impact information on EIF3S6IPP2

• Three structurally related protein complexes, the COP9 signalosome, the proteasome lid, and the eukaryotic translation initiation factor 3, are revealing new insights into developmental processes and into cell cycle control in healthy cells and cells exposed to genotoxic stress [3].
• The purified complex could rescue Met-tRNAiMet binding to 40S ribosomes in defective extracts from a prt1 mutant or extracts from which Nip1p had been depleted, indicating that it possesses a known biochemical activity of eIF3 [4].
• The 39-kilodalton subunit of eukaryotic translation initiation factor 3 is essential for the complex's integrity and for cell viability in Saccharomyces cerevisiae [5].
• The human protein HSPC021 interacts with Int-6 and is associated with eukaryotic translation initiation factor 3 [6].
• These protein motifs are also present in subunits of eIF3, of the lid of the 26 S proteasome, and of the COP9 signalosome [6].

Biological context of EIF3S6IPP2

• The Int-6 protein has been shown to be a subunit of eukaryotic translation initiation factor 3 (eIF3) and to play a role in the control of cell growth [6].
• Transfection experiments demonstrated that polyhistidine-tagged p42 protein, transiently expressed in human U20S cells, was incorporated into endogenous eIF3 [7].
• Originally described in plants as a regulator of photomorphogenesis, its purification and characterization from mammalian cells revealed significant sequence homologies to subunits of the 26S proteasome lid complex, as well as of the eukaryotic translation initiation factor 3 [8].

Anatomical context of EIF3S6IPP2

• Eukaryotic translation initiation factor 3 (eIF3), which plays an essential role in initiation of protein synthesis, was purified from rabbit reticulocyte lysates using an assay that specifically measures its ability to stimulate the binding of Met-tRNAf (as a Met-tRNAf.eIF2.GTP ternary complex) to 40 S ribosomal subunits [9].
• A differentially expressed gene identified by SSH, the p40 subunit of eukaryotic translation initiation factor 3 (eIF3), was localized to 8q23 and found to be highly amplified and overexpressed in the breast and prostate cancer cell lines studied [1].
• Externalization and recognition by macrophages of large subunit of eukaryotic translation initiation factor 3 in apoptotic cells [10].
• In this paper, we report our surprising findings that about 20% of p170 is associated with membranes while the remaining portion is located in the cytoplasm presumably in the eIF3 complex [2].

Other interactions of EIF3S6IPP2

• Recent studies indicate that Int6 is a multifaceted protein involved in the regulation of protein translation and degradation through binding with three complexes: the eukaryotic translation initiation factor 3, the proteasome regulatory lid, and the constitutive photomorphogenesis 9 signalosome [11].
• A functional link between Disrupted-In-Schizophrenia 1 and the eukaryotic translation initiation factor 3 [12].

Analytical, diagnostic and therapeutic context of EIF3S6IPP2

• Biochemical characterization of mammalian translation initiation factor 3 (eIF3). Molecular cloning reveals that p110 subunit is the mammalian homologue of Saccharomyces cerevisiae protein Prt1 [9].

References