Translational infidelity and human cancer: role of the PTI-1 oncogene.
Several components of the eukaryotic protein synthesis apparatus have been associated with oncogenic transformation of cells. Altered expression of translation elongation factor 1 alpha (EF-1 alpha), a core component of protein synthesis and closely related sequences have been linked with transformed phenotypes by several independent studies, in diverse systems. A dominant acting oncogene, prostate tumor inducing gene-1 (PTI-1) has provided further evidence for this link. PTI-1 appears to be a hybrid molecule with components derived from both prokaryotic and eukaryotic origins. The predicted protein coding moiety represents an EF-1 alpha molecule, truncated N-terminal to amino acid residue 68 and having six additional point mutations. This coding sequence is fused to a 5' untranslated region (UTR) showing strongest homology to ribosomal RNA derived from Mycoplasma hyopneumoniae. Expression studies using the cloned cDNA in nude mouse tumor formation assays have confirmed the oncogenic nature of the molecule. A broad spectrum of tumor derived cell lines, from varied tissue sources and blood samples from patients having confirmed prostate carcinoma, all scored positive for expression of PTI-1, while corresponding normal tissues or blood samples were negative. Based on its near identity to EF-1 alpha, it is proposed that PTI-1 represents a new class of oncogene whose transforming capacity probably arises through mechanisms including: (i) protein translational infidelity, resulting in the synthesis of mutant polypeptides due to loss of proofreading function during peptide chain elongation, (ii) by its association with and alteration of the cytoskeleton, (iii) by impinging on one particular or several different signal transduction pathways through its properties as a G-protein.
Gopalkrishnan
R V
RV
Department of Neurosurgery, Columbia University, College of Physicians and Surgeons, Herbert Irving Comprehensive Cancer Center, New York, NY 10032, USA.
Su
Z Z
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Goldstein
N I
NI
Fisher
P B
PB
D000595:Amino Acid Sequence; D000818:Animals; D016375:Antisense Elements (Genetics) / Q000235:genetics; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D003001:Cloning, Molecular; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000235:genetics*; D015513:Oncogene Proteins / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D020648:Peptide Elongation Factor 1; D011471:Prostatic Neoplasms / Q000235:genetics / Q000556:secondary; D014176:Protein Biosynthesis; D014407:Tumor Cells, Cultured
D016375:Antisense Elements (Genetics); D014408:Biomarkers, Tumor; C094814:EEF1A1 protein, human; D015513:Oncogene Proteins; D020648:Peptide Elongation Factor 1