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Oncogenic effect of delta deletion in v-Jun does not result from uncoupling Jun from JNK signaling

Oncogene volumeĀ 22,Ā pages 498ā€“506 (2003)Cite this article

Abstract

The protein encoded by the v-Jun oncogene shows increased transforming activity compared to c-Jun, its normal cellular counterpart. One major determinant of this increased transforming activity is an in-frame deletion of a region near the amino-terminus of the protein. This region, referred to as the delta domain, functions as a docking site for Jun N-terminal kinase (JNK), the mitogen-activated protein (MAP) kinase that phosphorylates c-Jun to regulate its transcriptional properties. As a consequence of this deletion, v-Jun is unresponsive to JNK signaling, and it is widely believed that it is the uncoupling of v-Jun from JNK signaling that underlies the oncogenic effects of the delta-domain deletion; however, this idea has never been directly tested. Here we use JNK overexpression as well as alanine scanning mutagenesis to test this idea. Point mutants that are uncoupled from JNK signaling do not show enhanced transforming activity, suggesting that disruption of the Junā€“JNK interaction is not the mechanism by which the delta-domain deletion enhances transforming activity. Consistent with this idea, we have generated a panel of point mutants that show markedly enhanced transforming activity, despite the fact that they do not perturb the ability of JNK to either dock with or phosphorylate c-Jun in vitro or in vivo. The fact that these mutants cluster in a small region suggests the existence of an additional regulator of Jun function whose activity is disrupted by mutations in this region.

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References

  • Adler V, Franklin CC and Kraft AS . (1992). Proc. Natl. Acad. Sci. USA, 89, 5341ā€“5345.

  • Akagi T, Shishido T, Murata K and Hanafusa H . (2000). Proc. Natl. Acad. Sci. USA, 97, 7290ā€“7295.

  • Baichwal VR and Tjian R . (1990). Cell, 63, 815ā€“825.

  • Baichwal VR, Park A and Tjian R . (1992). Genes Dev., 6, 1493ā€“1502.

  • Bardwell L, Cook JG, Voora D, Baggott DM, Martinez AR and Thorner J . (1998a). Genes Dev., 12, 2887ā€“2898.

  • Bardwell L, Cook JG, Zhu-Shimoni JX, Voora D and Thorner J . (1998b). Proc. Natl. Acad. Sci. USA, 95, 15400ā€“15405.

  • Black EJ, Catling AD, Woodgett JR, Kilbey A and Gillespie DA . (1994). Oncogene, 9, 2363ā€“2368.

  • Bos TJ, Monteclaro FS, Mitsunobu F, Ball Jr AR, Chang CH, Nishimura T and Vogt PK . (1990). Genes Dev., 4, 1677ā€“1687.

  • Castellazzi M, Dangy JP, Mechta F, Hirai S, Yaniv M, Samarut J, Lassailly A and Brun G . (1990). Oncogene, 5, 1541ā€“1547.

  • Cavalieri F, Ruscio T, Tinoco R, Benedict S, Davis C and Vogt PK . (1985). Virology, 143, 680ā€“683.

  • Claret FX, Hibi M, Dhut S, Toda T and Karin M . (1996). Nature, 383, 453ā€“457.

  • Cook JG, Bardwell L and Thorner J . (1997). Nature, 390, 85ā€“88.

  • Dai T, Rubie E, Franklin CC, Kraft A, Gillespie DA, Avruch J, Kyriakis JM and Woodgett JR . (1995). Oncogene, 10, 849ā€“855.

  • Derijard B, Hibi M, Wu IH, Barrett T, Su B, Deng T, Karin M and Davis RJ . (1994). Cell, 76, 1025ā€“1037.

  • Fantz DA, Jacobs D, Glossip D and Kornfeld K . (2001). J. Biol. Chem., 276, 27256ā€“27265.

  • Fu S, Bottoli I, Goller M and Vogt PK . (1999). Proc. Natl. Acad. Sci. USA, 96, 5716ā€“5721.

  • Gupta S, Barrett T, Whitmarsh AJ, Cavanagh J, Sluss HK, Derijard B and Davis RJ . (1996). EMBO J., 15, 2760ā€“2770.

  • Havarstein LS, Morgan IM, Wong WY and Vogt PK . (1992). Proc. Natl. Acad. Sci. USA, 89, 618ā€“622.

  • Hibi M, Lin A, Smeal T, Minden A and Karin M . (1993). Genes Dev., 7, 2135ā€“2148.

  • Jacobs D, Glossip D, Xing H, Muslin AJ and Kornfeld K . (1999). Genes Dev., 13, 163ā€“175.

  • Kallunki T, Deng T, Hibi M and Karin M . (1996). Cell, 87, 929ā€“939.

  • Kallunki T, Su B, Tsigelny I, Sluss HK, Derijard B, Moore G, Davis R and Karin M . (1994). Genes Dev., 8, 2996ā€“3007.

  • Kilbey A, Black EJ, Unlu M and Gillespie DA . (1996). Oncogene, 12, 2409ā€“2418.

  • Madhani HD, Styles CA and Fink GR . (1997). Cell, 91, 673ā€“684.

  • Maki Y, Bos TJ, Davis C, Starbuck M and Vogt PK . (1987). Proc. Natl. Acad. Sci. USA, 84, 2848ā€“2852.

  • May GH, Allen KE, Clark W, Funk M and Gillespie DA . (1998a). J. Biol. Chem., 273, 33429ā€“33435.

  • May GH, Funk M, Black EJ, Clark W, Hussain S, Woodgett JR and Gillespie DA . (1998b). Curr. Biol., 8, 117ā€“120.

  • Pearson G, Robinson F, Beers Gibson T, Xu BE, Karandikar M, Berman K and Cobb MH . (2001). Endocrinol. Rev., 22, 153ā€“183.

  • Pulverer BJ, Hughes K, Franklin CC, Kraft AS, Leevers SJ and Woodgett JR . (1993). Oncogene, 8, 407ā€“415.

  • Pulverer BJ, Kyriakis JM, Avruch J, Nikolakaki E and Woodgett JR . (1991). Nature, 353, 670ā€“674.

  • Smeal T, Binetruy B, Mercola DA, Birrer M and Karin M . (1991). Nature, 354, 494ā€“496.

  • Smeal T, Binetruy B, Mercola D, Grover-Bardwick A, Heidecker G, Rapp UR and Karin M . (1992). Mol. Cell. Biol., 12, 3507ā€“3513.

  • Ui M, Sonobe MH, Ito T, Murakami M, Okazaki S, Takada M, Sato T and Iba H . (1998). FEBS Lett., 429, 289ā€“294.

  • Vogt PK . (2001). Oncogene, 20, 2365ā€“2377.

  • Yang SH, Galanis A and Sharrocks AD . (1999). Mol. Cell. Biol., 19, 4028ā€“4038.

  • Yang SH, Whitmarsh AJ, Davis RJ and Sharrocks AD . (1998). EMBO J., 17, 1740ā€“1749.

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Acknowledgements

We thank Bruce Carter for his helpful suggestions. We thank T Akagi and PK Vogt for providing molecular clones. AS was supported by NIH training Grant T32CA009582. This work was supported by NIH Grant CA64118 (RW).

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Authors and Affiliations

  1. Department of Biochemistry, Vanderbilt University, Nashville, 37232, TN, USA

    Amy Sprowles

  2. Division of Hematology/Oncology and the UC Davis Cancer Center, UC Davis School of Medicine, Sacramento, 95817, CA, USA

    Ron Wisdom

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  1. Amy Sprowles
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  2. Ron Wisdom
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Correspondence to Ron Wisdom.

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Sprowles, A., Wisdom, R. Oncogenic effect of delta deletion in v-Jun does not result from uncoupling Jun from JNK signaling. Oncogene 22, 498ā€“506 (2003). https://doi.org/10.1038/sj.onc.1206165

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