A novel transcript encoded within the 10-kb first intron of the human p53 tumor suppressor gene (D17S2179E) is induced during differentiation of myeloid leukemia cells.
Two promoters were previously shown to map to the 5'-end of the human p53 gene. p53p1 was located upstream of the first exon and is responsible for transcription of the major p53 mRNA species. p53p2 is a stronger promoter than p53p1 and was located within the 10, 738-bp first intron, approximately 1000 bp downstream of exon 1. mRNA transcripts that initiated from p53p2 were previously identified in HL-60 cells by primer extension analysis and were observed to increase in abundance during differentiation of HL-60 cells to granulocytes. By screening a cDNA library with a probe derived from sequences downstream of the p53p2 start site, we have cloned and characterized a cDNA that represents a mRNA that appears to have been initiated from the p53p2 promoter. We have designated the gene encoding this transcript Hp53int1 (the GDB designation is D17S2179E). The cDNA is 1125 bp and is polyadenylated downstream from a consensus poly(A) addition site. The entire 1125 bp is derived from intron 1 of the p53 gene, with no introns having been removed. The cDNA contains no major open reading frame although reading frame +1 contains a relatively low abundance of stop codons compared to the other two reading frames and could possibly encode a protein of 119 amino acids. Analysis of the +1 reading frame shows a region of high homology to a portion of the DNA-binding domain of NF-kappaB. These results indicate that a novel polyadenylated transcript is encoded by the first intron of the human p53 gene. Hp53int1 may be a pseudogene for a gene that may have encoded a DNA-binding protein. Alternatively, the transcript may have a function, since RNA transcripts of this gene are present in a number of human cells and their levels are induced during terminal differentiation of myeloid leukemia cells such as HL-60 and U937.
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Department of Biological Sciences, University of South Carolina, Columbia 29208, USA. Reisman@biol.sc.edu
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D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000235:genetics; D015973:Gene Expression Regulation, Leukemic; D016158:Genes, p53; D018922:HL-60 Cells; D006801:Humans; D007438:Introns / Q000235:genetics*; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000737:chemistry; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics*; D012334:RNA, Neoplasm / Q000235:genetics*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D016328:NF-kappa B; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm