Loss of responsiveness of an AP1-related factor, PEBP1, to 12-O-tetradecanoylphorbol-13-acetate after transformation of NIH 3T3 cells by the Ha-ras oncogene (original) (raw)

Abstract

The function of the A element (nucleotides 5107 to 5130) of the polyomavirus enhancer is augumented in NIH 3T3 cells by a tumor-promoting phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA). One of its targets is an AP1 consensus sequence motif recognized by a nuclear factor, PEBP1. In Ha-ras-transformed NIH 3T3 cells, however, A element function was not enhanced by TPA treatment, and at the same time PEBP1 was not detected in the nuclear extract by a mobility shift assay. PEBP1 was not detected in either the extract from NIH 3T3 cells treated in vivo with a protein kinase inhibitor, staurosporine, or the extract from NIH 3T3 cells after treatment in vitro with phosphatase. These results suggest that PEBP1 is required to be properly phosphorylated for DNA binding and that it is underphosphorylated, possibly due to the downregulation of protein kinase C in Ha-ras-transformed cells. In addition, we observed that PEBP2, which bound to the A element adjacent to PEBP1, was converted to apparently related PEBP3 when conditions favored underphosphorylation.

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  1. Alonso T., Morgan R. O., Marvizon J. C., Zarbl H., Santos E. Malignant transformation by ras and other oncogenes produces common alterations in inositol phospholipid signaling pathways. Proc Natl Acad Sci U S A. 1988 Jun;85(12):4271–4275. doi: 10.1073/pnas.85.12.4271. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Angel P., Allegretto E. A., Okino S. T., Hattori K., Boyle W. J., Hunter T., Karin M. Oncogene jun encodes a sequence-specific trans-activator similar to AP-1. Nature. 1988 Mar 10;332(6160):166–171. doi: 10.1038/332166a0. [DOI] [PubMed] [Google Scholar]
  3. Angel P., Imagawa M., Chiu R., Stein B., Imbra R. J., Rahmsdorf H. J., Jonat C., Herrlich P., Karin M. Phorbol ester-inducible genes contain a common cis element recognized by a TPA-modulated trans-acting factor. Cell. 1987 Jun 19;49(6):729–739. doi: 10.1016/0092-8674(87)90611-8. [DOI] [PubMed] [Google Scholar]
  4. Baeuerle P. A., Baltimore D. Activation of DNA-binding activity in an apparently cytoplasmic precursor of the NF-kappa B transcription factor. Cell. 1988 Apr 22;53(2):211–217. doi: 10.1016/0092-8674(88)90382-0. [DOI] [PubMed] [Google Scholar]
  5. Ballester R., Rosen O. M. Fate of immunoprecipitable protein kinase C in GH3 cells treated with phorbol 12-myristate 13-acetate. J Biol Chem. 1985 Dec 5;260(28):15194–15199. [PubMed] [Google Scholar]
  6. Benjamin C. W., Tarpley W. G., Gorman R. R. Loss of platelet-derived growth factor-stimulated phospholipase activity in NIH-3T3 cells expressing the EJ-ras oncogene. Proc Natl Acad Sci U S A. 1987 Jan;84(2):546–550. doi: 10.1073/pnas.84.2.546. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bishop J. M. The molecular genetics of cancer. Science. 1987 Jan 16;235(4786):305–311. doi: 10.1126/science.3541204. [DOI] [PubMed] [Google Scholar]
  8. Bohmann D., Bos T. J., Admon A., Nishimura T., Vogt P. K., Tjian R. Human proto-oncogene c-jun encodes a DNA binding protein with structural and functional properties of transcription factor AP-1. Science. 1987 Dec 4;238(4832):1386–1392. doi: 10.1126/science.2825349. [DOI] [PubMed] [Google Scholar]
  9. Bos T. J., Bohmann D., Tsuchie H., Tjian R., Vogt P. K. v-jun encodes a nuclear protein with enhancer binding properties of AP-1. Cell. 1988 Mar 11;52(5):705–712. doi: 10.1016/0092-8674(88)90408-4. [DOI] [PubMed] [Google Scholar]
  10. Castagna M., Takai Y., Kaibuchi K., Sano K., Kikkawa U., Nishizuka Y. Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor-promoting phorbol esters. J Biol Chem. 1982 Jul 10;257(13):7847–7851. [PubMed] [Google Scholar]
  11. Dignam J. D., Lebovitz R. M., Roeder R. G. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 1983 Mar 11;11(5):1475–1489. doi: 10.1093/nar/11.5.1475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Fleischman L. F., Chahwala S. B., Cantley L. ras-transformed cells: altered levels of phosphatidylinositol-4,5-bisphosphate and catabolites. Science. 1986 Jan 24;231(4736):407–410. doi: 10.1126/science.3001936. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Hannun Y. A., Bell R. M. Lysosphingolipids inhibit protein kinase C: implications for the sphingolipidoses. Science. 1987 Feb 6;235(4789):670–674. doi: 10.1126/science.3101176. [DOI] [PubMed] [Google Scholar]
  15. Herbomel P., Bourachot B., Yaniv M. Two distinct enhancers with different cell specificities coexist in the regulatory region of polyoma. Cell. 1984 Dec;39(3 Pt 2):653–662. doi: 10.1016/0092-8674(84)90472-0. [DOI] [PubMed] [Google Scholar]
  16. Housey G. M., Johnson M. D., Hsiao W. L., O'Brian C. A., Murphy J. P., Kirschmeier P., Weinstein I. B. Overproduction of protein kinase C causes disordered growth control in rat fibroblasts. Cell. 1988 Feb 12;52(3):343–354. doi: 10.1016/s0092-8674(88)80027-8. [DOI] [PubMed] [Google Scholar]
  17. Huang C. L., Ives H. E. Growth inhibition by protein kinase C late in mitogenesis. 1987 Oct 29-Nov 4Nature. 329(6142):849–850. doi: 10.1038/329849a0. [DOI] [PubMed] [Google Scholar]
  18. Imler J. L., Schatz C., Wasylyk C., Chatton B., Wasylyk B. A Harvey-ras responsive transcription element is also responsive to a tumour-promoter and to serum. Nature. 1988 Mar 17;332(6161):275–278. doi: 10.1038/332275a0. [DOI] [PubMed] [Google Scholar]
  19. Inoue M., Kishimoto A., Takai Y., Nishizuka Y. Studies on a cyclic nucleotide-independent protein kinase and its proenzyme in mammalian tissues. II. Proenzyme and its activation by calcium-dependent protease from rat brain. J Biol Chem. 1977 Nov 10;252(21):7610–7616. [PubMed] [Google Scholar]
  20. Jones R. H., Moreno S., Nurse P., Jones N. C. Expression of the SV40 promoter in fission yeast: identification and characterization of an AP-1-like factor. Cell. 1988 May 20;53(4):659–667. doi: 10.1016/0092-8674(88)90581-8. [DOI] [PubMed] [Google Scholar]
  21. Kamata T., Sullivan N. F., Wooten M. W. Reduced protein kinase C activity in a ras-resistant cell line derived from Ki-MSV transformed cells. Oncogene. 1987 Mar;1(1):37–46. [PubMed] [Google Scholar]
  22. Kikkawa U., Takai Y., Tanaka Y., Miyake R., Nishizuka Y. Protein kinase C as a possible receptor protein of tumor-promoting phorbol esters. J Biol Chem. 1983 Oct 10;258(19):11442–11445. [PubMed] [Google Scholar]
  23. Kolesnick R. N., Clegg S. 1,2-Diacylglycerols, but not phorbol esters, activate a potential inhibitory pathway for protein kinase C in GH3 pituitary cells. Evidence for involvement of a sphingomyelinase. J Biol Chem. 1988 May 15;263(14):6534–6537. [PubMed] [Google Scholar]
  24. Kryszke M. H., Piette J., Yaniv M. Induction of a factor that binds to the polyoma virus A enhancer on differentiation of embryonal carcinoma cells. Nature. 1987 Jul 16;328(6127):254–256. doi: 10.1038/328254a0. [DOI] [PubMed] [Google Scholar]
  25. Lacal J. C., Moscat J., Aaronson S. A. Novel source of 1,2-diacylglycerol elevated in cells transformed by Ha-ras oncogene. Nature. 1987 Nov 19;330(6145):269–272. doi: 10.1038/330269a0. [DOI] [PubMed] [Google Scholar]
  26. Laimins L. A., Gruss P., Pozzatti R., Khoury G. Characterization of enhancer elements in the long terminal repeat of Moloney murine sarcoma virus. J Virol. 1984 Jan;49(1):183–189. doi: 10.1128/jvi.49.1.183-189.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Lee W., Haslinger A., Karin M., Tjian R. Activation of transcription by two factors that bind promoter and enhancer sequences of the human metallothionein gene and SV40. Nature. 1987 Jan 22;325(6102):368–372. doi: 10.1038/325368a0. [DOI] [PubMed] [Google Scholar]
  28. Lee W., Mitchell P., Tjian R. Purified transcription factor AP-1 interacts with TPA-inducible enhancer elements. Cell. 1987 Jun 19;49(6):741–752. doi: 10.1016/0092-8674(87)90612-x. [DOI] [PubMed] [Google Scholar]
  29. Maki Y., Bos T. J., Davis C., Starbuck M., Vogt P. K. Avian sarcoma virus 17 carries the jun oncogene. Proc Natl Acad Sci U S A. 1987 May;84(9):2848–2852. doi: 10.1073/pnas.84.9.2848. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Mueller C. R., Mes-Masson A. M., Bouvier M., Hassell J. A. Location of sequences in polyomavirus DNA that are required for early gene expression in vivo and in vitro. Mol Cell Biol. 1984 Dec;4(12):2594–2609. doi: 10.1128/mcb.4.12.2594. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Parries G., Hoebel R., Racker E. Opposing effects of a ras oncogene on growth factor-stimulated phosphoinositide hydrolysis: desensitization to platelet-derived growth factor and enhanced sensitivity to bradykinin. Proc Natl Acad Sci U S A. 1987 May;84(9):2648–2652. doi: 10.1073/pnas.84.9.2648. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Persons D. A., Wilkison W. O., Bell R. M., Finn O. J. Altered growth regulation and enhanced tumorigenicity of NIH 3T3 fibroblasts transfected with protein kinase C-I cDNA. Cell. 1988 Feb 12;52(3):447–458. doi: 10.1016/s0092-8674(88)80037-0. [DOI] [PubMed] [Google Scholar]
  33. Piette J., Hirai S., Yaniv M. Constitutive synthesis of activator protein 1 transcription factor after viral transformation of mouse fibroblasts. Proc Natl Acad Sci U S A. 1988 May;85(10):3401–3405. doi: 10.1073/pnas.85.10.3401. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Piette J., Yaniv M. Two different factors bind to the alpha-domain of the polyoma virus enhancer, one of which also interacts with the SV40 and c-fos enhancers. EMBO J. 1987 May;6(5):1331–1337. doi: 10.1002/j.1460-2075.1987.tb02372.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Rauscher F. J., 3rd, Cohen D. R., Curran T., Bos T. J., Vogt P. K., Bohmann D., Tjian R., Franza B. R., Jr Fos-associated protein p39 is the product of the jun proto-oncogene. Science. 1988 May 20;240(4855):1010–1016. doi: 10.1126/science.3130660. [DOI] [PubMed] [Google Scholar]
  36. Rodriguez-Pena A., Rozengurt E. Disappearance of Ca2+-sensitive, phospholipid-dependent protein kinase activity in phorbol ester-treated 3T3 cells. Biochem Biophys Res Commun. 1984 May 16;120(3):1053–1059. doi: 10.1016/s0006-291x(84)80213-2. [DOI] [PubMed] [Google Scholar]
  37. Santos E., Tronick S. R., Aaronson S. A., Pulciani S., Barbacid M. T24 human bladder carcinoma oncogene is an activated form of the normal human homologue of BALB- and Harvey-MSV transforming genes. Nature. 1982 Jul 22;298(5872):343–347. doi: 10.1038/298343a0. [DOI] [PubMed] [Google Scholar]
  38. Satake M., Furukawa K., Ito Y. Biological activities of oligonucleotides spanning the F9 point mutation within the enhancer region of polyomavirus DNA. J Virol. 1988 Mar;62(3):970–977. doi: 10.1128/jvi.62.3.970-977.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Veldman G. M., Lupton S., Kamen R. Polyomavirus enhancer contains multiple redundant sequence elements that activate both DNA replication and gene expression. Mol Cell Biol. 1985 Apr;5(4):649–658. doi: 10.1128/mcb.5.4.649. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Verma I. M., Sassone-Corsi P. Proto-oncogene fos: complex but versatile regulation. Cell. 1987 Nov 20;51(4):513–514. doi: 10.1016/0092-8674(87)90115-2. [DOI] [PubMed] [Google Scholar]
  41. Wasylyk B., Imler J. L., Chatton B., Schatz C., Wasylyk C. Negative and positive factors determine the activity of the polyoma virus enhancer alpha domain in undifferentiated and differentiated cell types. Proc Natl Acad Sci U S A. 1988 Nov;85(21):7952–7956. doi: 10.1073/pnas.85.21.7952. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Wasylyk C., Imler J. L., Perez-Mutul J., Wasylyk B. The c-Ha-ras oncogene and a tumor promoter activate the polyoma virus enhancer. Cell. 1987 Feb 13;48(3):525–534. doi: 10.1016/0092-8674(87)90203-0. [DOI] [PubMed] [Google Scholar]
  43. Wasylyk C., Imler J. L., Wasylyk B. Transforming but not immortalizing oncogenes activate the transcription factor PEA1. EMBO J. 1988 Aug;7(8):2475–2483. doi: 10.1002/j.1460-2075.1988.tb03094.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Wolfman A., Macara I. G. Elevated levels of diacylglycerol and decreased phorbol ester sensitivity in ras-transformed fibroblasts. Nature. 1987 Jan 22;325(6102):359–361. doi: 10.1038/325359a0. [DOI] [PubMed] [Google Scholar]
  45. Wolfman A., Wingrove T. G., Blackshear P. J., Macara I. G. Down-regulation of protein kinase C and of an endogenous 80-kDa substrate in transformed fibroblasts. J Biol Chem. 1987 Dec 5;262(34):16546–16552. [PubMed] [Google Scholar]
  46. Yamaguchi Y., Satake M., Ito Y. Two overlapping sequence motifs within the polyomavirus enhancer are independently the targets of stimulation by both the tumor promoter 12-O-tetradecanoylphorbol-13-acetate and the Ha-ras oncogene. J Virol. 1989 Mar;63(3):1040–1048. doi: 10.1128/jvi.63.3.1040-1048.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]