Disease relevance of ETF1

• We have evaluated ETF1 as a candidate myeloid tumor suppressor gene by analysis of the human acute myeloid leukemia cell line HL60, and of patients suffering from malignant myeloid diseases with cytogenetically-defined abnormalities of chromosome 5 [1].
• The aa sequence of the human protein was deduced from a 2.3-kb cDNA (TB3-1) isolated from an adenocarcinoma T84 cell line cDNA library [2].
• An Escherichia coli system for protein synthesis in vitro with purified components was used to study the accuracy of termination by RF1 and RF2 in the presence or absence of RF3 [3].
• DNA strand breaks induced by estradiol metabolites were measured by the conversion of supercoiled phage phiX-174 RF1 DNA to open circular and linear forms [4].
• We had previously shown that several transcription factors of the ethylene (ET) response factor (ERF) family were induced with different but overlapping kinetics following challenge of Arabidopsis (Arabidopsis thaliana) with Pseudomonas syringae pv tomato DC3000 (avrRpt2) [5].

High impact information on ETF1

• Free RF3 is in vivo stably bound to GDP, and ribosomes in complex with RF1 or RF2 act as guanine nucleotide exchange factors (GEF) [6].
• The crystal structure of human eukaryotic release factor eRF1--mechanism of stop codon recognition and peptidyl-tRNA hydrolysis [7].
• The crystal structure of human eRF1 to 2.8 A resolution, combined with mutagenesis analyses of the universal GGQ motif, reveals the molecular mechanism of release factor activity [7].
• The amino-acid sequence of the eRF1 family is highly conserved [8].
• Further, we describe a novel complex that contains the NMD factors SMG-1 and Upf1, and the translation termination release factors eRF1 and eRF3 (SURF) [9].

Chemical compound and disease context of ETF1

• The expression patterns of the translation mechanism, namely of the elongation factors eEF1A1 and eEF1A2, and of the termination factors eRF1 and eRF3, were studied in the breast cancer cell line MCF-7 by real-time quantitative reverse transcription-polymerase chain reaction after a 24-h treatment with NaBu and TSA [10].

Biological context of ETF1

• The human genome contains four ETF1 (eukaryotic translation termination factor 1) homologous sequences, localized on chromosomes 5, 6, 7 and X, and corresponding to a functional gene on chromosome 5 and three processed pseudogenes on the other chromosomes [11].
• 1. A microsatellite marker (D5S500) was identified in intron 7 of the functional ETF1 gene providing its exact position in the 5q31 band [11].
• An additional upstream promoter containing positive and negative regulatory elements also regulated ETF1 gene expression [12].
• The catalytic subunit of protein phosphatase 2A associates with the translation termination factor eRF1 [13].
• Human release factor eRF1: structural organisation of the unique functional gene on chromosome 5 and of the three processed pseudogenes [14].

Anatomical context of ETF1

• Fluorescence in situ hybridization analysis revealed hemizygous loss of the ETF1 locus in HL60 cells and in four of five leukemic samples, but no inactivating mutations were identified by sequencing of the remaining ETF1 allele [1].
• The release factor eRF1 terminates protein biosynthesis by recognizing stop codons at the A site of the ribosome and stimulating peptidyl-tRNA bond hydrolysis at the peptidyl transferase center [7].
• This is the first description of this code, previously found only in bacteria and mitochondria, in a eukaryotic nuclear genome. eRF1 has evolved strikingly convergently in lineages with variant genetic codes [15].
• Mouse embryos at different stages of development were cocultured with human oviduct cells or cultured in the presence of oviduct-derived embryotrophic factor-1, -2, and -3 (ETF-1, -2, and -3) for various amounts of time within the preimplantation period [16].
• Western analysis showed TB3 localization in both the cytoplasm and nucleus, but not in membranes [17].

Associations of ETF1 with chemical compounds

• To unravel the region of human eukaryotic release factor 1 (eRF1) that is close to stop codons within the ribosome, we used mRNAs containing a single photoactivatable 4-thiouridine (s(4)U) residue in the first position of stop or control sense codons [18].
• The invariant uridine of stop codons contacts the conserved NIKSR loop of human eRF1 in the ribosome [18].
• The levels were compared with levels of total hemolytic complement and immunochemical determinations of Cl1 and C3 [19].
• Finally, increased puromycin sensitivity was observed after depletion of eRF1 from the stalled ribosome complex, consistent with inhibition of peptidyl-tRNA hydrolysis resulting from an eRF1-uORF2 peptidyl-tRNA interaction [20].
• BDNF treatment of high TrkB-expressing TB8 (Tet-) and TB3 (Tet-) cells blocked drug-induced cell death in a dose-dependent manner [21].

Regulatory relationships of ETF1

• Finally, our data indicate that the expression level of eRF3a controls the formation of the termination complex by modulating eRF1 protein stability [22].

Other interactions of ETF1

• We also found that eRF3a depletion reduced the intracellular level of eRF1 protein by affecting its stability [22].
• By deletion analysis, the binding domains were found to be located within the 50 N-terminal amino acids of PP2Ac, and between amino acid residues 338 and 381 in the C-terminal part of human eRF1 [13].
• Among the new remarkable features revealed by structural studies, is the mimicry of the tRNA molecule by elongation factor G, ribosomal recycling factor and the eukaryotic release factor 1 [23].

Analytical, diagnostic and therapeutic context of ETF1

• ETF1 genomic or cDNA probes were mapped by fluorescence in situ hybridization to 5q31, 6p21, 7q11 and Xp11.4-->p11 [11].
• Assignment of the human translation termination factor 1 (ETF1) to 5q31.1 and of the proximal marker D5S1995 by radiation hybrid mapping [24].
• Molecular cloning of a novel member of the eukaryotic polypeptide chain-releasing factors (eRF). Its identification as eRF3 interacting with eRF1 [25].
• Real-time quantitative RT-PCR analysis showed tissue-specific expression of ETF1 transcripts in mouse tissues [12].
• We have undertaken a systematic analysis of the interactions between the human eRF1 and eRF3 employing a yeast two-hybrid assay [26].

References