Alternative titles; symbols
HGNC Approved Gene Symbol: GSPT1
Cytogenetic location: 16p13.13 Genomic coordinates (GRCh38): 16:11,868,128-11,916,654 (from NCBI)
Kikuchi et al. (1988) isolated a gene from a yeast genomic library that could complement a temperature-sensitive mutant of Saccharomyces cerevisiae. The gene, termed GST1, seemed to be essential for the G1- to S-phase transition in the yeast cell cycle. The gene product appeared to be a GTP-binding protein of molecular mass 76,565 Da with 38% identity in amino acid sequence with the alpha subunit of elongation factor-1 (130590). Hoshino et al. (1989) cloned the human equivalent from a cDNA library.
Hoshino et al. (1998) cloned mouse Gspt1. The deduced 635-amino acid protein has a unique N terminus and a conserved C-terminal eukaryotic elongation factor-1-alpha-like domain. The mouse and human Gspt1 proteins share 94% sequence identity. RT-PCR analysis indicated expression of Gspt1 in all mouse tissues examined.
Eukaryotic RF1 (ETF1; 600285) and RF3 are involved in translation termination. In vitro, RF1 catalyzes the release of the polypeptide chain without any stop codon specificity; the GTP-binding protein RF3 confers GTP dependence to the termination process and stimulates RF1 activity. Le Goff et al. (1997) used tRNA-mediated nonsense suppression of different stop codons in a CAT reporter gene to analyze the polypeptide chain release factor activities of recombinant human RF1 and RF3 proteins overexpressed in human cells. Using a CAT assay, they measured the competition between the suppressor tRNA and the release factors when a stop codon was present in the ribosomal A site. Regardless of which of the 3 stop codons was present in the CAT open reading frame, the overexpression of RF1 alone markedly decreased translational read-through by suppressor tRNA. Thus, Le Goff et al. (1997) concluded that RF1 has intrinsic antisuppressor activity. The levels of antisuppression when both RF1 and RF3 were overexpressed were almost the same as those when RF1 was overexpressed alone, suggesting that RF1-RF3 complex-mediated termination may be controlled by the expression level of RF1. Overexpression of RF3 alone had an inhibitory effect on CAT gene expression. CAT mRNA stability studies suggested that RF3 inhibits gene expression at the transcriptional level. Le Goff et al. (1997) suggested that RF3 may perform other functions, including the stimulation of RF1 activity, in vivo.
Hoshino et al. (1998) found that expression of Gspt1 by Swiss 3T3 cells increased with serum or phorbol ester stimulation. By coimmunoprecipitation and yeast 2-hybrid analyses, they found interaction between mouse Gspt1 and human eRF1. Hoshino et al. (1998) hypothesized that Gspt1, in a binary complex with eRF1, functions as a polypeptide chain release factor.
Alkalaeva et al. (2006) reconstituted eukaryotic translation initiation, elongation, and termination processes in vitro on a model mRNA encoding a tetrapeptide followed by a UAA stop codon using individual 40S and 60S ribosomal subunits and the complete set of individual initiation, elongation, and release factors. They found that binding of human ERF1 and ERF3A and GTP to the ribosomal pretermination complex induced a structural rearrangement characterized by a 2-nucleotide forward shift of the toeprint attributed to the pretermination complex. Subsequent GTP hydrolysis was required for rapid hydrolysis of peptidyl tRNA in the pretermination complex. Cooperativity between ERF1 and ERF3A in ensuring fast peptidyl-tRNA hydrolysis required the ERF3A-binding C-terminal domain of ERF1.
Using a yeast 2-hybrid screen and in vitro and in vivo binding assays, including reciprocal immunoprecipitation assays, Tompkins et al. (2006) showed that GSPT1 bound the p19(ARF) isoform of CDKN2A (600160), but not the p16(INK4A) isoform.
By nonradioactive in situ hybridization, Ozawa et al. (1992) mapped the GSPT1 gene, the human homolog of the yeast gene GST1, to human chromosome 16p13.1. Southern blot hybridization with a panel of human-rodent somatic cells confirmed the localization of the GSPT1 gene on chromosome 16 and also showed the existence of a homologous gene on the X chromosome (GSPT2; 300418). They pointed out that a breakpoint for nonrandom chromosome rearrangements has been found in the region of GSPT1 in patients with acute nonlymphocytic leukemia.
Alkalaeva, E. Z., Pisarev, A. V., Frolova, L. Y., Kisselev, L. L., Pestova, T. V. In vitro reconstitution of eukaryotic translation reveals cooperativity between release factors eRF1 and eRF3. Cell 125: 1125-1136, 2006. [PubMed: 16777602] [Full Text: https://doi.org/10.1016/j.cell.2006.04.035]
Hoshino, S., Imai, M., Mizutani, M., Kikuchi, Y., Hanaoka, F., Ui, M., Katada, T. Molecular cloning of a novel member of the eukaryotic polypeptide chain-releasing factors (eRF): its identification as eRF3 interacting with eRF1. J. Biol. Chem. 273: 22254-22259, 1998. [PubMed: 9712840] [Full Text: https://doi.org/10.1074/jbc.273.35.22254]
Hoshino, S., Miyazawa, H., Enomoto, T., Hanaoka, F., Kikuchi, Y., Kikuchi, A., Ui, M. A human homologue of the yeast GST1 gene codes for a GTP-binding protein and is expressed in a proliferation-dependent manner in mammalian cells. EMBO J. 8: 3807-3814, 1989. [PubMed: 2511002] [Full Text: https://doi.org/10.1002/j.1460-2075.1989.tb08558.x]
Kikuchi, Y., Shimatake, H., Kikucki, A. A yeast gene required for the G1-to-S transition encodes a protein containing an A-kinase target site and GTPase domain. EMBO J. 7: 1175-1182, 1988. [PubMed: 2841115] [Full Text: https://doi.org/10.1002/j.1460-2075.1988.tb02928.x]
Le Goff, X., Philippe, M., Jean-Jean, O. Overexpression of human release factor 1 alone has an antisuppressor effect in human cells. Molec. Cell Biol. 17: 3164-3172, 1997. [PubMed: 9154815] [Full Text: https://doi.org/10.1128/MCB.17.6.3164]
Ozawa, K., Murakami, Y., Eki, T., Yokoyama, K., Soeda, E., Hoshino, S., Ui, M., Hanaoka, F. Mapping of the human GSPT1 gene, a human homolog of the yeast GST1 gene, to chromosomal band 16p13.1. Somat. Cell Molec. Genet. 18: 189-194, 1992. [PubMed: 1574740] [Full Text: https://doi.org/10.1007/BF01233164]
Tompkins, V., Hagen, J., Zediak, V. P., Quelle, D. E. Identification of novel ARF binding proteins by two-hybrid screening. Cell Cycle 5: 641-646, 2006. [PubMed: 16582619]