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. 1993 Apr;13(4):2524–2535. doi: 10.1128/mcb.13.4.2524

Mutations in the Drosophila gene encoding ribosomal protein S6 cause tissue overgrowth.

M J Stewart 1, R Denell 1
PMCID: PMC359579  PMID: 8384310

Abstract

We have characterized two P-element-induced, lethal mutations in Drosophila melanogaster which affect the larval hemocytes, mediators of the insect immune response. Each mutant displays larval melanotic tumors characteristic of mutations affecting the insect cellular immune system, and the moribund animals develop grossly hypertrophied hematopoietic organs because of increased cell proliferation and extra rounds of endoreduplication in some hematopoietic cells. Surprisingly, these mutations are due to P element insertions in the 5' regulatory region of the Drosophila gene encoding ribosomal protein S6 and cause a reduction of S6 transcript abundance in mutant larvae.

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Selected References

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  1. Arkhipova I. R., Ilyin Y. V. Properties of promoter regions of mdg1 Drosophila retrotransposon indicate that it belongs to a specific class of promoters. EMBO J. 1991 May;10(5):1169–1177. doi: 10.1002/j.1460-2075.1991.tb08057.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Atchison M. L., Meyuhas O., Perry R. P. Localization of transcriptional regulatory elements and nuclear factor binding sites in mouse ribosomal protein gene rpL32. Mol Cell Biol. 1989 May;9(5):2067–2074. doi: 10.1128/mcb.9.5.2067. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bellen H. J., O'Kane C. J., Wilson C., Grossniklaus U., Pearson R. K., Gehring W. J. P-element-mediated enhancer detection: a versatile method to study development in Drosophila. Genes Dev. 1989 Sep;3(9):1288–1300. doi: 10.1101/gad.3.9.1288. [DOI] [PubMed] [Google Scholar]
  4. Brown S. J., Rhoads D. D., Stewart M. J., Van Slyke B., Chen I. T., Johnson T. K., Denell R. E., Roufa D. J. Ribosomal protein S14 is encoded by a pair of highly conserved, adjacent genes on the X chromosome of Drosophila melanogaster. Mol Cell Biol. 1988 Oct;8(10):4314–4321. doi: 10.1128/mcb.8.10.4314. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chan Y. L., Wool I. G. The primary structure of rat ribosomal protein S6. J Biol Chem. 1988 Feb 25;263(6):2891–2896. [PubMed] [Google Scholar]
  6. Cooley L., Kelley R., Spradling A. Insertional mutagenesis of the Drosophila genome with single P elements. Science. 1988 Mar 4;239(4844):1121–1128. doi: 10.1126/science.2830671. [DOI] [PubMed] [Google Scholar]
  7. Dorer D. R., Anane-Firempong A., Christensen A. C. Ribosomal protein S14 is not responsible for the Minute phenotype associated with the M(1)7C locus in Drosophila melanogaster. Mol Gen Genet. 1991 Nov;230(1-2):8–11. doi: 10.1007/BF00290642. [DOI] [PubMed] [Google Scholar]
  8. Flotow H., Thomas G. Substrate recognition determinants of the mitogen-activated 70K S6 kinase from rat liver. J Biol Chem. 1992 Feb 15;267(5):3074–3078. [PubMed] [Google Scholar]
  9. Gateff E. Malignant neoplasms of genetic origin in Drosophila melanogaster. Science. 1978 Jun 30;200(4349):1448–1459. doi: 10.1126/science.96525. [DOI] [PubMed] [Google Scholar]
  10. Hanratty W. P., Ryerse J. S. A genetic melanotic neoplasm of Drosophila melanogaster. Dev Biol. 1981 Apr 30;83(2):238–249. doi: 10.1016/0012-1606(81)90470-x. [DOI] [PubMed] [Google Scholar]
  11. Hariharan N., Perry R. P. Functional dissection of a mouse ribosomal protein promoter: significance of the polypyrimidine initiator and an element in the TATA-box region. Proc Natl Acad Sci U S A. 1990 Feb;87(4):1526–1530. doi: 10.1073/pnas.87.4.1526. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Heinze H., Arnold H. H., Fischer D., Kruppa J. The primary structure of the human ribosomal protein S6 derived from a cloned cDNA. J Biol Chem. 1988 Mar 25;263(9):4139–4144. [PubMed] [Google Scholar]
  13. Hultmark D., Klemenz R., Gehring W. J. Translational and transcriptional control elements in the untranslated leader of the heat-shock gene hsp22. Cell. 1986 Feb 14;44(3):429–438. doi: 10.1016/0092-8674(86)90464-2. [DOI] [PubMed] [Google Scholar]
  14. Kay M. A., Zhang J. Y., Jacobs-Lorena M. Identification and germline transformation of the ribosomal protein rp21 gene of Drosophila: complementation analysis with the Minute QIII locus reveals nonidentity. Mol Gen Genet. 1988 Aug;213(2-3):354–358. doi: 10.1007/BF00339602. [DOI] [PubMed] [Google Scholar]
  15. Klämbt C., Müller S., Lützelschwab R., Rossa R., Totzke F., Schmidt O. The Drosophila melanogaster l(2)gl gene encodes a protein homologous to the cadherin cell-adhesion molecule family. Dev Biol. 1989 Jun;133(2):425–436. doi: 10.1016/0012-1606(89)90046-8. [DOI] [PubMed] [Google Scholar]
  16. Kongsuwan K., Yu Q., Vincent A., Frisardi M. C., Rosbash M., Lengyel J. A., Merriam J. A Drosophila Minute gene encodes a ribosomal protein. Nature. 1985 Oct 10;317(6037):555–558. doi: 10.1038/317555a0. [DOI] [PubMed] [Google Scholar]
  17. Lazaris-Karatzas A., Montine K. S., Sonenberg N. Malignant transformation by a eukaryotic initiation factor subunit that binds to mRNA 5' cap. Nature. 1990 Jun 7;345(6275):544–547. doi: 10.1038/345544a0. [DOI] [PubMed] [Google Scholar]
  18. Leer R. J., van Raamsdonk-Duin M. M., Molenaar C. M., Cohen L. H., Mager W. H., Planta R. J. The structure of the gene coding for the phosphorylated ribosomal protein S10 in yeast. Nucleic Acids Res. 1982 Oct 11;10(19):5869–5878. doi: 10.1093/nar/10.19.5869. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Lefevre G., Johnson T. K. Evidence for a Sex-Linked Haplo-Inviable Locus in the Cut-Singed Region of DROSOPHILA MELANOGASTER. Genetics. 1973 Aug;74(4):633–645. doi: 10.1093/genetics/74.4.633. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Madjar J. J., Fournier A. Starvation-induced alterations of ribosomal protein phosphorylation in Bombyx mori L. Evidence for different phosphorylation kinetics in free and membrane-bound ribosomes. Eur J Biochem. 1987 Mar 16;163(3):577–582. doi: 10.1111/j.1432-1033.1987.tb10906.x. [DOI] [PubMed] [Google Scholar]
  21. Mager W. H. Control of ribosomal protein gene expression. Biochim Biophys Acta. 1988 Jan 25;949(1):1–15. doi: 10.1016/0167-4781(88)90048-6. [DOI] [PubMed] [Google Scholar]
  22. Mahoney P. A., Weber U., Onofrechuk P., Biessmann H., Bryant P. J., Goodman C. S. The fat tumor suppressor gene in Drosophila encodes a novel member of the cadherin gene superfamily. Cell. 1991 Nov 29;67(5):853–868. doi: 10.1016/0092-8674(91)90359-7. [DOI] [PubMed] [Google Scholar]
  23. Mechler B. M., Strand D., Kalmes A., Merz R., Schmidt M., Török I. Drosophila as a model system for molecular analysis of tumorigenesis. Environ Health Perspect. 1991 Jun;93:63–71. doi: 10.1289/ehp.919363. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. O'Hare K., Rubin G. M. Structures of P transposable elements and their sites of insertion and excision in the Drosophila melanogaster genome. Cell. 1983 Aug;34(1):25–35. doi: 10.1016/0092-8674(83)90133-2. [DOI] [PubMed] [Google Scholar]
  25. Olsen A. S., Triemer D. F., Sanders M. M. Dephosphorylation of S6 and expression of the heat shock response in Drosophila melanogaster. Mol Cell Biol. 1983 Nov;3(11):2017–2027. doi: 10.1128/mcb.3.11.2017. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Palen E., Traugh J. A. Phosphorylation of ribosomal protein S6 by cAMP-dependent protein kinase and mitogen-stimulated S6 kinase differentially alters translation of globin mRNA. J Biol Chem. 1987 Mar 15;262(8):3518–3523. [PubMed] [Google Scholar]
  27. Pardee A. B. G1 events and regulation of cell proliferation. Science. 1989 Nov 3;246(4930):603–608. doi: 10.1126/science.2683075. [DOI] [PubMed] [Google Scholar]
  28. 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]
  29. Poole S. J., Kauvar L. M., Drees B., Kornberg T. The engrailed locus of Drosophila: structural analysis of an embryonic transcript. Cell. 1985 Jan;40(1):37–43. doi: 10.1016/0092-8674(85)90306-x. [DOI] [PubMed] [Google Scholar]
  30. Qian S., Hongo S., Jacobs-Lorena M. Antisense ribosomal protein gene expression specifically disrupts oogenesis in Drosophila melanogaster. Proc Natl Acad Sci U S A. 1988 Dec;85(24):9601–9605. doi: 10.1073/pnas.85.24.9601. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Rizki T. M., Rizki R. M. Topology of the caudal fat body of the tumor-w mutant of Drosophila melanogaster. J Invertebr Pathol. 1974 Jul;24(1):37–40. doi: 10.1016/0022-2011(74)90161-x. [DOI] [PubMed] [Google Scholar]
  32. Sturgill T. W., Wu J. Recent progress in characterization of protein kinase cascades for phosphorylation of ribosomal protein S6. Biochim Biophys Acta. 1991 May 17;1092(3):350–357. doi: 10.1016/s0167-4889(97)90012-4. [DOI] [PubMed] [Google Scholar]
  33. Thomas G., Thomas G., Luther H. Transcriptional and translational control of cytoplasmic proteins after serum stimulation of quiescent Swiss 3T3 cells. Proc Natl Acad Sci U S A. 1981 Sep;78(9):5712–5716. doi: 10.1073/pnas.78.9.5712. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Vaslet C. A., O'Connell P., Izquierdo M., Rosbash M. Isolation and mapping of a cloned ribosomal protein gene of Drosophila melanogaster. Nature. 1980 Jun 26;285(5767):674–676. doi: 10.1038/285674a0. [DOI] [PubMed] [Google Scholar]
  35. Watson K. L., Johnson T. K., Denell R. E. Lethal(1) aberrant immune response mutations leading to melanotic tumor formation in Drosophila melanogaster. Dev Genet. 1991;12(3):173–187. doi: 10.1002/dvg.1020120302. [DOI] [PubMed] [Google Scholar]
  36. Woods D. F., Bryant P. J. The discs-large tumor suppressor gene of Drosophila encodes a guanylate kinase homolog localized at septate junctions. Cell. 1991 Aug 9;66(3):451–464. doi: 10.1016/0092-8674(81)90009-x. [DOI] [PubMed] [Google Scholar]
  37. Yamamoto A., Araki T., Counis M. F. Decrease of DNA per cell during development of the lens in chickens. Histochemistry. 1990;94(3):293–296. doi: 10.1007/BF00266630. [DOI] [PubMed] [Google Scholar]

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