Disease relevance of EIF3S10

• We now show that NAF specifically binds to purified p185 expressed in baculovirus [1].
• To determine the mechanism of this interaction we have used a vaccinia virus/bacteriophage T7-based transient gene expression system to induce production of normal and kinase-deficient forms of p185 in the absence and presence of EGF receptors [2].
• Species-specific replication of simian virus 40 DNA in vitro requires the p180 subunit of human DNA polymerase alpha-primase [3].
• First, the results demonstrate that the ectopic expression of the p185 Bcr-Abl fusion protein induced hemoglobin in the acute myeloid leukemia (AML) HL-60 cells [4].
• In these, we used (1) the human acute myelogenous leukemia (AML) HL-60 cells that are stably transfected with the bcr-abl gene (HL-60/Bcr-Abl) and express p185 Bcr-Abl; and (2) the chronic myelogenous leukemia (CML)-blast crisis K562 cells, which have endogenous expression of p210 Bcr-Abl [5].

High impact information on EIF3S10

• Here we report that the 20S proteasome endoproteolytically cleaves the translation initiation factors eIF4G, a subunit of eIF4F, and eIF3a, a subunit of eIF3 [6].
• Using an immunoperoxidase technique, we stained archival formalin-fixed, paraffin-embedded tissue sections with a monoclonal antibody to the 185-kilodalton protein product (p185) of the HER-2/neu gene [7].
• We report here that incubation of Rat-1 cells with EGF stimulates tyrosine phosphorylation of p185 [8].
• Certain amino acid substitutions at position 664 in the transmembrane domain of the neu oncogene-encoded p185 protein product are known to cause malignant transformation of cells [9].
• The following lines of evidence collectively imply that a candidate ligand of the neu-encoded oncoprotein is secreted by ras-transformed fibroblasts: Medium conditioned by ras transformants is able to induce down-modulation of the neu-encoded p185 and to activate its intrinsic tyrosine kinase activity in vitro [10].

Chemical compound and disease context of EIF3S10

• The cytoplasmic domain of p180 was found to contain a serine residue(s) that was phosphorylated both in vivo and in vitro by activated protein kinase C. p180 was purified by subjecting solubilized membrane proteins from a human osteosarcoma cell line to immunoaffinity chromatography and gel filtration [11].
• We have examined the effects of herbimycin A and several analogues on p185, the tyrosine kinase encoded by the erbB2 gene in human breast cancer cells [12].
• Using the human breast cancer cell lines T47D and MCF7, we found that the arrest of cell growth induced by a steroid-depleted medium was accompanied by a strong increase of c-erbB-2 mRNA and of the c-erbB-2-encoded p185 protein [13].
• In a screening for new growth factors released by melanoma cells, we found that the p185-phosphorylating capacity of a medium conditioned by a melanoma cell line was due to the secretion of heregulin, a ligand for the human epidermal growth factor receptor (HER) family of receptor tyrosine kinases [14].
• CONCLUSIONS: Selective and efficient killing of human lung adenocarcinoma cells can be achieved in vitro using c-erbB-2/p185-directed therapy [15].

Biological context of EIF3S10

• Assignment1 of the p150 subunit of the eukaryotic initiation factor 3A gene (EIF3A) to human chromosome band 10q26 by in situ hybridisation [16].
• A stretch of 10 amino acid-residues was repeated 21 times in KIAA0139, and a homologous sequence of 76-78 nucleotides was found repeated 6 times in the untranslated region of KIAA0125 [17].
• The rat neu oncogene encodes a cell surface glycoprotein, p185, that possesses tyrosine kinase activity [18].
• p185, the product of the neu/erbB2 proto-oncogene, is oncogenically activated by a point mutation that substitutes glutamic acid for valine in the transmembrane domain of the protein [19].
• Two cellular proteins (p160 and p180) were phosphorylated on tyrosine only during mitosis [20].

Anatomical context of EIF3S10

• The rat embryonal fibroblast cell line (Rat-1) appears to express both EGFR and cellular p185 polypeptides [18].
• Morphological studies demonstrated that on the cell surface p180 was concentrated in coated pits, whereas inside the cell it was found in endosomes as suggested by its colocalization with the transferrin receptor [11].
• HL-60/Bcr-Abl cells, with ectopic expression of p185 Bcr-Abl tyrosine kinase (TK), and K562 cells, with endogenous expression of p210 Bcr-Abl TK, display a high degree of resistance against antileukemic drug-induced apoptosis (G. Fang et al., Blood, 96: 2246-2256, 2000) [21].
• All antisera are highly reactive with a Mr 180,000 (p180) P-glycoprotein contained in membranes of HL60 cells isolated for resistance to vincristine (HL60/Vinc) [22].
• In this study, we have identified a protein with a molecular mass approximately 180 kDa from rabbit liver cytosol (designated p180), which binds preferentially to the GTP- and guanosine 5'-3-O-(thio)triphosphate-bound forms of Cdc42 [23].

Associations of EIF3S10 with chemical compounds

• Collectively, these data demonstrate that EGF mediates phosphorylation of p185 at tyrosine as well as serine/threonine through cellular kinases by a receptor-specific mechanism [18].
• TAb 250 inhibited BT-474 cells but did not alter p185 phosphotyrosine content or increase receptor turnover in these cells [24].
• Studies with cell lines transfected with erbB2 containing defined deletions indicated that susceptibility to the depletion of p185 by herbimycin and its analogues required the domain encoded by amino acids 751-971 [12].
• In this article, we tested this hypothesis and investigated whether eIF3 p170 mediates mimosine effect on mRNA translation [25].
• The purified topoisomerase II migrated on sodium dodecyl sulfate-polyacrylamide gel electrophoresis as two bands with apparent molecular masses of 180 (p180) and 170 kDa (p170); both proteins unknotted P4 DNA in an ATP-dependent manner and displayed amsacrine-stimulated covalent attachment to DNA [26].

Regulatory relationships of EIF3S10

• It has been suggested that uPA in cancer cells is up regulated by the p 185 kD form of the HER-2/neu oncogene [27].

Other interactions of EIF3S10

• Moreover, the immunohistochemical detection of the transmembrane proteins EGFR, p-185 and p-148 by oncogene overexpression and c-myc oncogene were undertaken in 425 breast cancers [28].
• L-mimosine, a plant amino acid, can reversibly block mammalian cells at late G1 phase and has been found to affect translation of mRNAs of the cyclin-dependent kinase inhibitor p27, eIF3a (eIF3 p170), and ribonucleotide reductase M2 [29].
• The cleavage of eIF4G or eIF3a differentially affects the assembly of ribosomal preinitiation complexes on different cellular and viral mRNAs in an in vitro system containing pure components [6].

Analytical, diagnostic and therapeutic context of EIF3S10

• IMPLICATIONS: The fact that p185 immunoreactivity is rarely heterogeneous is encouraging, both for the potential use of HER-2/neu-related proteins as serum tumor markers and for innovative therapies targeted at p185 expression [7].
• PATIENTS AND METHODS: Paraffin-embedded tumors from 315 consecutive primary breast cancer patients were screened for c-erbB-2 protein (p185) overexpression by immunohistochemistry using the monoclonal antibody CB11 [30].
• Using a double monoclonal antibody capture enzyme-linked immunosorbent assay for p185, activity was detected in conditioned media from cultures of SK-BR-3 cells [31].
• Immunoblotting of the samples prepared from metaphase-synchronized HeLa cells did not have a p180 band, but did exhibit a band with a higher molecular weight [32].
• In order to physically localize these cells we have stained frozen sections of human thymus with antibodies to CD45RO (p180), and CD45RA (p205/P220), as well as with CD1 and HLA class I to define cortical and medullary areas, respectively [33].

References