Abstract
We previously identified a putative T cell oncogene on chromosome 11 near a translocation t(11;14)(p15;q11) in a human T cell tumour. The gene is transcribed from distinct promoters which have unrelated sequences, which occur within close but distinct methylation-free islands and which allow cell specific production of mRNA. The alternative first exons each contain a protein initiation codon from which two species of protein can be made, differing by only a single amino acid. The protein sequence is highly conserved between man and mouse (98%) and the same single codon difference between alternative first exons is also conserved. This is, therefore, a new form of eukaryotic gene organization from which similar proteins can be made from distinct mRNA species.
Full text
PDF











Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Andreadis A., Gallego M. E., Nadal-Ginard B. Generation of protein isoform diversity by alternative splicing: mechanistic and biological implications. Annu Rev Cell Biol. 1987;3:207–242. doi: 10.1146/annurev.cb.03.110187.001231. [DOI] [PubMed] [Google Scholar]
- Baer R., Forster A., Lavenir I., Rabbitts T. H. Immunoglobulin VH genes are transcribed by T cells in association with a new 5' exon. J Exp Med. 1988 Jun 1;167(6):2011–2016. doi: 10.1084/jem.167.6.2011. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Belyavsky A., Vinogradova T., Rajewsky K. PCR-based cDNA library construction: general cDNA libraries at the level of a few cells. Nucleic Acids Res. 1989 Apr 25;17(8):2919–2932. doi: 10.1093/nar/17.8.2919. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bernard O., Larsen C. J., Hampe A., Mauchauffé M., Berger R., Mathieu-Mahul D. Molecular mechanisms of a t(8;14)(q24;q11) translocation juxtaposing c-myc and TcR-alpha genes in a T-cell leukaemia: involvement of a V alpha internal heptamer. Oncogene. 1988 Feb;2(2):195–200. [PubMed] [Google Scholar]
- Boehm T., Baer R., Lavenir I., Forster A., Waters J. J., Nacheva E., Rabbitts T. H. The mechanism of chromosomal translocation t(11;14) involving the T-cell receptor C delta locus on human chromosome 14q11 and a transcribed region of chromosome 11p15. EMBO J. 1988 Feb;7(2):385–394. doi: 10.1002/j.1460-2075.1988.tb02825.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Boehm T., Buluwela L., Williams D., White L., Rabbitts T. H. A cluster of chromosome 11p13 translocations found via distinct D-D and D-D-J rearrangements of the human T cell receptor delta chain gene. EMBO J. 1988 Jul;7(7):2011–2017. doi: 10.1002/j.1460-2075.1988.tb03040.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Boehm T., Mengle-Gaw L., Kees U. R., Spurr N., Lavenir I., Forster A., Rabbitts T. H. Alternating purine-pyrimidine tracts may promote chromosomal translocations seen in a variety of human lymphoid tumours. EMBO J. 1989 Sep;8(9):2621–2631. doi: 10.1002/j.1460-2075.1989.tb08402.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Croce C. M. Role of chromosome translocations in human neoplasia. Cell. 1987 Apr 24;49(2):155–156. doi: 10.1016/0092-8674(87)90552-6. [DOI] [PubMed] [Google Scholar]
- Durnam D. M., Perrin F., Gannon F., Palmiter R. D. Isolation and characterization of the mouse metallothionein-I gene. Proc Natl Acad Sci U S A. 1980 Nov;77(11):6511–6515. doi: 10.1073/pnas.77.11.6511. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Döffinger R., Pawlita M., Sczakiel G. Electrotransfection of human lymphoid and myeloid cell lines. Nucleic Acids Res. 1988 Dec 23;16(24):11840–11840. doi: 10.1093/nar/16.24.11840. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Finger L. R., Huebner K., Cannizzaro L. A., McLeod K., Nowell P. C., Croce C. M. Chromosomal translocation in T-cell leukemia line HUT 78 results in a MYC fusion transcript. Proc Natl Acad Sci U S A. 1988 Dec;85(23):9158–9162. doi: 10.1073/pnas.85.23.9158. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gorman C. M., Moffat L. F., Howard B. H. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982 Sep;2(9):1044–1051. doi: 10.1128/mcb.2.9.1044. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hall C. V., Jacob P. E., Ringold G. M., Lee F. Expression and regulation of Escherichia coli lacZ gene fusions in mammalian cells. J Mol Appl Genet. 1983;2(1):101–109. [PubMed] [Google Scholar]
- Hamlyn P. H., Rabbitts T. H. Translocation joins c-myc and immunoglobulin gamma 1 genes in a Burkitt lymphoma revealing a third exon in the c-myc oncogene. Nature. 1983 Jul 14;304(5922):135–139. doi: 10.1038/304135a0. [DOI] [PubMed] [Google Scholar]
- Knudson A. G., Jr Hereditary cancer, oncogenes, and antioncogenes. Cancer Res. 1985 Apr;45(4):1437–1443. [PubMed] [Google Scholar]
- Kretsinger R. H. Structure and evolution of calcium-modulated proteins. CRC Crit Rev Biochem. 1980;8(2):119–174. doi: 10.3109/10409238009105467. [DOI] [PubMed] [Google Scholar]
- LeFranc M. P., Forster A., Baer R., Stinson M. A., Rabbitts T. H. Diversity and rearrangement of the human T cell rearranging gamma genes: nine germ-line variable genes belonging to two subgroups. Cell. 1986 Apr 25;45(2):237–246. doi: 10.1016/0092-8674(86)90388-0. [DOI] [PubMed] [Google Scholar]
- McGuire E. A., Hockett R. D., Pollock K. M., Bartholdi M. F., O'Brien S. J., Korsmeyer S. J. The t(11;14)(p15;q11) in a T-cell acute lymphoblastic leukemia cell line activates multiple transcripts, including Ttg-1, a gene encoding a potential zinc finger protein. Mol Cell Biol. 1989 May;9(5):2124–2132. doi: 10.1128/mcb.9.5.2124. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nabeshima Y., Fujii-Kuriyama Y., Muramatsu M., Ogata K. Alternative transcription and two modes of splicing results in two myosin light chains from one gene. Nature. 1984 Mar 22;308(5957):333–338. doi: 10.1038/308333a0. [DOI] [PubMed] [Google Scholar]
- Neumann E., Schaefer-Ridder M., Wang Y., Hofschneider P. H. Gene transfer into mouse lyoma cells by electroporation in high electric fields. EMBO J. 1982;1(7):841–845. doi: 10.1002/j.1460-2075.1982.tb01257.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rabbitts T. H., Boehm T., Mengle-Gaw L. Chromosomal abnormalities in lymphoid tumours: mechanism and role in tumour pathogenesis. Trends Genet. 1988 Nov;4(11):300–304. doi: 10.1016/0168-9525(88)90106-0. [DOI] [PubMed] [Google Scholar]
- Shima E. A., Le Beau M. M., McKeithan T. W., Minowada J., Showe L. C., Mak T. W., Minden M. D., Rowley J. D., Diaz M. O. Gene encoding the alpha chain of the T-cell receptor is moved immediately downstream of c-myc in a chromosomal 8;14 translocation in a cell line from a human T-cell leukemia. Proc Natl Acad Sci U S A. 1986 May;83(10):3439–3443. doi: 10.1073/pnas.83.10.3439. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smale S. T., Baltimore D. The "initiator" as a transcription control element. Cell. 1989 Apr 7;57(1):103–113. doi: 10.1016/0092-8674(89)90176-1. [DOI] [PubMed] [Google Scholar]
- Van Straaten J. P., Rabbitts T. H. The c-myc protein is associated with the nuclear matrix through specific metal interaction. Oncogene Res. 1987 Aug;1(3):221–228. [PubMed] [Google Scholar]
- Young R. A., Hagenbüchle O., Schibler U. A single mouse alpha-amylase gene specifies two different tissue-specific mRNAs. Cell. 1981 Feb;23(2):451–458. doi: 10.1016/0092-8674(81)90140-9. [DOI] [PubMed] [Google Scholar]