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. 1992 Jan 15;89(2):618–622. doi: 10.1073/pnas.89.2.618

Mutations in the Jun delta region suggest an inverse correlation between transformation and transcriptional activation.

L S Håvarstein 1, I M Morgan 1, W Y Wong 1, P K Vogt 1
PMCID: PMC48290  PMID: 1309952

Abstract

The viral Jun protein (v-Jun) transforms chicken embryo fibroblasts (CEF) more effectively than its cellular counterpart (c-Jun). In certain cell types v-Jun is also a stronger transcriptional activator than c-Jun. These functional differences between v-Jun and c-Jun result from a deletion in v-Jun (referred to as "delta deletion") that seems to weaken the interaction of Jun with a negative cellular regulator molecule. These observations suggested that the oncogenicity of v-Jun may be due to an enhanced ability to activate transcription of target genes. To test this hypothesis, we constructed several deletions in the delta domain of chicken c-Jun and determined their transforming and transactivating properties. Surprisingly, we found an inverse correlation between the ability of the mutants to transform CEF and to transactivate the collagenase and transin promoters in CEF. In contrast, there was no significant effect of the delta mutations in c-Jun on transactivation in F9 murine embryonal carcinoma cells. The function of the delta region is therefore cell-type specific. The inverse correlation between transformation and transactivation in CEF suggests that the strong growth-promoting effect of v-Jun may be related to a failure to activate the transcription of growth attenuating genes.

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Selected References

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

  1. 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]
  2. Angel P., Smeal T., Meek J., Karin M. Jun and v-jun contain multiple regions that participate in transcriptional activation in an interdependent manner. New Biol. 1989 Oct;1(1):35–43. [PubMed] [Google Scholar]
  3. Baichwal V. R., Park A., Tjian R. v-Src and EJ Ras alleviate repression of c-Jun by a cell-specific inhibitor. Nature. 1991 Jul 11;352(6331):165–168. doi: 10.1038/352165a0. [DOI] [PubMed] [Google Scholar]
  4. Baichwal V. R., Tjian R. Control of c-Jun activity by interaction of a cell-specific inhibitor with regulatory domain delta: differences between v- and c-Jun. Cell. 1990 Nov 16;63(4):815–825. doi: 10.1016/0092-8674(90)90147-7. [DOI] [PubMed] [Google Scholar]
  5. Binétruy B., Smeal T., Karin M. Ha-Ras augments c-Jun activity and stimulates phosphorylation of its activation domain. Nature. 1991 May 9;351(6322):122–127. doi: 10.1038/351122a0. [DOI] [PubMed] [Google Scholar]
  6. Bister K., Hayman M. J., Vogt P. K. Defectiveness of avian myelocytomatosis virus MC29: isolation of long-term nonproducer cultures and analysis of virus-specific polypeptide synthesis. Virology. 1977 Oct 15;82(2):431–448. doi: 10.1016/0042-6822(77)90017-4. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Bohmann D., Tjian R. Biochemical analysis of transcriptional activation by Jun: differential activity of c- and v-Jun. Cell. 1989 Nov 17;59(4):709–717. doi: 10.1016/0092-8674(89)90017-2. [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. Bos T. J., Monteclaro F. S., Mitsunobu F., Ball A. R., Jr, Chang C. H., Nishimura T., Vogt P. K. Efficient transformation of chicken embryo fibroblasts by c-Jun requires structural modification in coding and noncoding sequences. Genes Dev. 1990 Oct;4(10):1677–1687. doi: 10.1101/gad.4.10.1677. [DOI] [PubMed] [Google Scholar]
  11. Chiu R., Angel P., Karin M. Jun-B differs in its biological properties from, and is a negative regulator of, c-Jun. Cell. 1989 Dec 22;59(6):979–986. doi: 10.1016/0092-8674(89)90754-x. [DOI] [PubMed] [Google Scholar]
  12. Chiu R., Boyle W. J., Meek J., Smeal T., Hunter T., Karin M. The c-Fos protein interacts with c-Jun/AP-1 to stimulate transcription of AP-1 responsive genes. Cell. 1988 Aug 12;54(4):541–552. doi: 10.1016/0092-8674(88)90076-1. [DOI] [PubMed] [Google Scholar]
  13. Devary Y., Gottlieb R. A., Lau L. F., Karin M. Rapid and preferential activation of the c-jun gene during the mammalian UV response. Mol Cell Biol. 1991 May;11(5):2804–2811. doi: 10.1128/mcb.11.5.2804. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gaub M. P., Bellard M., Scheuer I., Chambon P., Sassone-Corsi P. Activation of the ovalbumin gene by the estrogen receptor involves the fos-jun complex. Cell. 1990 Dec 21;63(6):1267–1276. doi: 10.1016/0092-8674(90)90422-b. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Hughes S. H., Greenhouse J. J., Petropoulos C. J., Sutrave P. Adaptor plasmids simplify the insertion of foreign DNA into helper-independent retroviral vectors. J Virol. 1987 Oct;61(10):3004–3012. doi: 10.1128/jvi.61.10.3004-3012.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hughes S., Kosik E. Mutagenesis of the region between env and src of the SR-A strain of Rous sarcoma virus for the purpose of constructing helper-independent vectors. Virology. 1984 Jul 15;136(1):89–99. doi: 10.1016/0042-6822(84)90250-2. [DOI] [PubMed] [Google Scholar]
  18. Inoue J., Kerr L. D., Ransone L. J., Bengal E., Hunter T., Verma I. M. c-rel activates but v-rel suppresses transcription from kappa B sites. Proc Natl Acad Sci U S A. 1991 May 1;88(9):3715–3719. doi: 10.1073/pnas.88.9.3715. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kawai S., Nishizawa M. New procedure for DNA transfection with polycation and dimethyl sulfoxide. Mol Cell Biol. 1984 Jun;4(6):1172–1174. doi: 10.1128/mcb.4.6.1172. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kerr L. D., Miller D. B., Matrisian L. M. TGF-beta 1 inhibition of transin/stromelysin gene expression is mediated through a Fos binding sequence. Cell. 1990 Apr 20;61(2):267–278. doi: 10.1016/0092-8674(90)90807-q. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. Lamph W. W. Cross-coupling of AP-1 and intracellular hormone receptors. Cancer Cells. 1991 May;3(5):183–185. [PubMed] [Google Scholar]
  23. Lamph W. W., Wamsley P., Sassone-Corsi P., Verma I. M. Induction of proto-oncogene JUN/AP-1 by serum and TPA. Nature. 1988 Aug 18;334(6183):629–631. doi: 10.1038/334629a0. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. Muller D., Quantin B., Gesnel M. C., Millon-Collard R., Abecassis J., Breathnach R. The collagenase gene family in humans consists of at least four members. Biochem J. 1988 Jul 1;253(1):187–192. doi: 10.1042/bj2530187. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Nakabeppu Y., Ryder K., Nathans D. DNA binding activities of three murine Jun proteins: stimulation by Fos. Cell. 1988 Dec 2;55(5):907–915. doi: 10.1016/0092-8674(88)90146-8. [DOI] [PubMed] [Google Scholar]
  27. Pertovaara L., Sistonen L., Bos T. J., Vogt P. K., Keski-Oja J., Alitalo K. Enhanced jun gene expression is an early genomic response to transforming growth factor beta stimulation. Mol Cell Biol. 1989 Mar;9(3):1255–1262. doi: 10.1128/mcb.9.3.1255. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Quantin B., Breathnach R. Epidermal growth factor stimulates transcription of the c-jun proto-oncogene in rat fibroblasts. Nature. 1988 Aug 11;334(6182):538–539. doi: 10.1038/334538a0. [DOI] [PubMed] [Google Scholar]
  29. Ransone L. J., Visvader J., Wamsley P., Verma I. M. Trans-dominant negative mutants of Fos and Jun. Proc Natl Acad Sci U S A. 1990 May;87(10):3806–3810. doi: 10.1073/pnas.87.10.3806. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. 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]
  31. Raycroft L., Wu H. Y., Lozano G. Transcriptional activation by wild-type but not transforming mutants of the p53 anti-oncogene. Science. 1990 Aug 31;249(4972):1049–1051. doi: 10.1126/science.2144364. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Richardson P. M., Gilmore T. D. vRel is an inactive member of the Rel family of transcriptional activating proteins. J Virol. 1991 Jun;65(6):3122–3130. doi: 10.1128/jvi.65.6.3122-3130.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Ryseck R. P., Hirai S. I., Yaniv M., Bravo R. Transcriptional activation of c-jun during the G0/G1 transition in mouse fibroblasts. Nature. 1988 Aug 11;334(6182):535–537. doi: 10.1038/334535a0. [DOI] [PubMed] [Google Scholar]
  34. Sassone-Corsi P., Lamph W. W., Kamps M., Verma I. M. fos-associated cellular p39 is related to nuclear transcription factor AP-1. Cell. 1988 Aug 12;54(4):553–560. doi: 10.1016/0092-8674(88)90077-3. [DOI] [PubMed] [Google Scholar]
  35. Schüle R., Umesono K., Mangelsdorf D. J., Bolado J., Pike J. W., Evans R. M. Jun-Fos and receptors for vitamins A and D recognize a common response element in the human osteocalcin gene. Cell. 1990 May 4;61(3):497–504. doi: 10.1016/0092-8674(90)90531-i. [DOI] [PubMed] [Google Scholar]
  36. Schütte J., Viallet J., Nau M., Segal S., Fedorko J., Minna J. jun-B inhibits and c-fos stimulates the transforming and trans-activating activities of c-jun. Cell. 1989 Dec 22;59(6):987–997. doi: 10.1016/0092-8674(89)90755-1. [DOI] [PubMed] [Google Scholar]
  37. Su H. Y., Bos T. J., Monteclaro F. S., Vogt P. K. Jun inhibits myogenic differentiation. Oncogene. 1991 Oct;6(10):1759–1766. [PubMed] [Google Scholar]
  38. Vogt P. K., Bos T. J. jun: oncogene and transcription factor. Adv Cancer Res. 1990;55:1–35. doi: 10.1016/s0065-230x(08)60466-2. [DOI] [PubMed] [Google Scholar]
  39. Yang-Yen H. F., Chambard J. C., Sun Y. L., Smeal T., Schmidt T. J., Drouin J., Karin M. Transcriptional interference between c-Jun and the glucocorticoid receptor: mutual inhibition of DNA binding due to direct protein-protein interaction. Cell. 1990 Sep 21;62(6):1205–1215. doi: 10.1016/0092-8674(90)90396-v. [DOI] [PubMed] [Google Scholar]

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