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. 1993 Jul 1;90(13):6071–6075. doi: 10.1073/pnas.90.13.6071

A gene in the chromosomal region 3p21 with greatly reduced expression in lung cancer is similar to the gene for ubiquitin-activating enzyme.

K Kok 1, R Hofstra 1, A Pilz 1, A van den Berg 1, P Terpstra 1, C H Buys 1, B Carritt 1
PMCID: PMC46869  PMID: 8327486

Abstract

The chromosomal region 3p21 is thought to be the site of a lung tumor suppressor gene. We recently cloned a gene from this region that has greatly reduced expression in almost all lung tumor cell lines examined, in spite of being widely expressed in a variety of other tumor and nontumor cell types. We report here the sequence of this gene and show that it has significant homology to the genes encoding the ubiquitin-activating enzymes of three species, including humans. This suggests it is a second, autosomal member of this gene family in humans and may play a role in the ubiquitin conjugation pathway, which is of central importance in all eukaryotes.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Borthakur D., Basche M., Buikema W. J., Borthakur P. B., Haselkorn R. Expression, nucleotide sequence and mutational analysis of two open reading frames in the nif gene region of Anabaena sp. strain PCC7120. Mol Gen Genet. 1990 Apr;221(2):227–234. doi: 10.1007/BF00261725. [DOI] [PubMed] [Google Scholar]
  2. Brauch H., Johnson B., Hovis J., Yano T., Gazdar A., Pettengill O. S., Graziano S., Sorenson G. D., Poiesz B. J., Minna J. Molecular analysis of the short arm of chromosome 3 in small-cell and non-small-cell carcinoma of the lung. N Engl J Med. 1987 Oct 29;317(18):1109–1113. doi: 10.1056/NEJM198710293171803. [DOI] [PubMed] [Google Scholar]
  3. Carritt B., Kok K., van den Berg A., Osinga J., Pilz A., Hofstra R. M., Davis M. B., van der Veen A. Y., Rabbitts P. H., Gulati K. A gene from human chromosome region 3p21 with reduced expression in small cell lung cancer. Cancer Res. 1992 Mar 15;52(6):1536–1541. [PubMed] [Google Scholar]
  4. Ciechanover A., DiGiuseppe J. A., Bercovich B., Orian A., Richter J. D., Schwartz A. L., Brodeur G. M. Degradation of nuclear oncoproteins by the ubiquitin system in vitro. Proc Natl Acad Sci U S A. 1991 Jan 1;88(1):139–143. doi: 10.1073/pnas.88.1.139. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Ciechanover A., Finley D., Varshavsky A. Ubiquitin dependence of selective protein degradation demonstrated in the mammalian cell cycle mutant ts85. Cell. 1984 May;37(1):57–66. doi: 10.1016/0092-8674(84)90300-3. [DOI] [PubMed] [Google Scholar]
  6. Finley D., Ciechanover A., Varshavsky A. Thermolability of ubiquitin-activating enzyme from the mammalian cell cycle mutant ts85. Cell. 1984 May;37(1):43–55. doi: 10.1016/0092-8674(84)90299-x. [DOI] [PubMed] [Google Scholar]
  7. Handley P. M., Mueckler M., Siegel N. R., Ciechanover A., Schwartz A. L. Molecular cloning, sequence, and tissue distribution of the human ubiquitin-activating enzyme E1. Proc Natl Acad Sci U S A. 1991 Jan 1;88(1):258–262. doi: 10.1073/pnas.88.1.258. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hatfield P. M., Callis J., Vierstra R. D. Cloning of ubiquitin activating enzyme from wheat and expression of a functional protein in Escherichia coli. J Biol Chem. 1990 Sep 15;265(26):15813–15817. [PubMed] [Google Scholar]
  9. Higgins D. G., Sharp P. M. CLUSTAL: a package for performing multiple sequence alignment on a microcomputer. Gene. 1988 Dec 15;73(1):237–244. doi: 10.1016/0378-1119(88)90330-7. [DOI] [PubMed] [Google Scholar]
  10. Jentsch S., Seufert W., Sommer T., Reins H. A. Ubiquitin-conjugating enzymes: novel regulators of eukaryotic cells. Trends Biochem Sci. 1990 May;15(5):195–198. doi: 10.1016/0968-0004(90)90161-4. [DOI] [PubMed] [Google Scholar]
  11. Kay G. F., Ashworth A., Penny G. D., Dunlop M., Swift S., Brockdorff N., Rastan S. A candidate spermatogenesis gene on the mouse Y chromosome is homologous to ubiquitin-activating enzyme E1. Nature. 1991 Dec 12;354(6353):486–489. doi: 10.1038/354486a0. [DOI] [PubMed] [Google Scholar]
  12. Kok K., Osinga J., Carritt B., Davis M. B., van der Hout A. H., van der Veen A. Y., Landsvater R. M., de Leij L. F., Berendsen H. H., Postmus P. E. Deletion of a DNA sequence at the chromosomal region 3p21 in all major types of lung cancer. Nature. 1987 Dec 10;330(6148):578–581. doi: 10.1038/330578a0. [DOI] [PubMed] [Google Scholar]
  13. Kozak M. An analysis of vertebrate mRNA sequences: intimations of translational control. J Cell Biol. 1991 Nov;115(4):887–903. doi: 10.1083/jcb.115.4.887. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kulka R. G., Raboy B., Schuster R., Parag H. A., Diamond G., Ciechanover A., Marcus M. A Chinese hamster cell cycle mutant arrested at G2 phase has a temperature-sensitive ubiquitin-activating enzyme, E1. J Biol Chem. 1988 Oct 25;263(30):15726–15731. [PubMed] [Google Scholar]
  15. Lee S. W., Tomasetto C., Sager R. Positive selection of candidate tumor-suppressor genes by subtractive hybridization. Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2825–2829. doi: 10.1073/pnas.88.7.2825. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. McGrath J. P., Jentsch S., Varshavsky A. UBA 1: an essential yeast gene encoding ubiquitin-activating enzyme. EMBO J. 1991 Jan;10(1):227–236. doi: 10.1002/j.1460-2075.1991.tb07940.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Mitchell M. J., Woods D. R., Tucker P. K., Opp J. S., Bishop C. E. Homology of a candidate spermatogenic gene from the mouse Y chromosome to the ubiquitin-activating enzyme E1. Nature. 1991 Dec 12;354(6353):483–486. doi: 10.1038/354483a0. [DOI] [PubMed] [Google Scholar]
  18. Naylor S. L., Johnson B. E., Minna J. D., Sakaguchi A. Y. Loss of heterozygosity of chromosome 3p markers in small-cell lung cancer. Nature. 1987 Oct 1;329(6138):451–454. doi: 10.1038/329451a0. [DOI] [PubMed] [Google Scholar]
  19. Nohno T., Kasai Y., Saito T. Cloning and sequencing of the Escherichia coli chlEN operon involved in molybdopterin biosynthesis. J Bacteriol. 1988 Sep;170(9):4097–4102. doi: 10.1128/jb.170.9.4097-4102.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Pearson W. R., Lipman D. J. Improved tools for biological sequence comparison. Proc Natl Acad Sci U S A. 1988 Apr;85(8):2444–2448. doi: 10.1073/pnas.85.8.2444. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Staden R. Computer methods to locate signals in nucleic acid sequences. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 2):505–519. doi: 10.1093/nar/12.1part2.505. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Takahashi E., Ayusawa D., Kaneda S., Itoh Y., Seno T., Hori T. The human ubiquitin-activating enzyme E1 gene (UBE1) mapped to band Xp11.3----p11.23 by fluorescence in situ hybridization. Cytogenet Cell Genet. 1992;59(4):268–269. doi: 10.1159/000133266. [DOI] [PubMed] [Google Scholar]
  24. Wierenga R. K., Terpstra P., Hol W. G. Prediction of the occurrence of the ADP-binding beta alpha beta-fold in proteins, using an amino acid sequence fingerprint. J Mol Biol. 1986 Jan 5;187(1):101–107. doi: 10.1016/0022-2836(86)90409-2. [DOI] [PubMed] [Google Scholar]
  25. Zacksenhaus E., Sheinin R. Molecular cloning of human A1S9 locus: an X-linked gene essential for progression through S phase of the cell cycle. Somat Cell Mol Genet. 1989 Nov;15(6):545–553. doi: 10.1007/BF01534915. [DOI] [PubMed] [Google Scholar]
  26. Zacksenhaus E., Sheinin R. Molecular cloning, primary structure and expression of the human X linked A1S9 gene cDNA which complements the ts A1S9 mouse L cell defect in DNA replication. EMBO J. 1990 Sep;9(9):2923–2929. doi: 10.1002/j.1460-2075.1990.tb07483.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Zacksenhaus E., Sheinin R., Wang H. S. Localization of the human A1S9 gene complementing the ts A1S9 mouse L-cell defect in DNA replication and cell cycle progression to Xp11.2----p11.4. Cytogenet Cell Genet. 1990;53(1):20–22. doi: 10.1159/000132887. [DOI] [PubMed] [Google Scholar]

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