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Mouse homologue of HOS (mHOS) is overexpressed in skin tumors and implicated in constitutive activation of NF-κB

Oncogene volume 21, pages 1501–1509 (2002)Cite this article

Abstract

NF-κB transcription factor is activated upon ubiquitination and subsequent proteolysis of its inhibitor IκB. The phosphorylation-dependent ubiquitination is mediated by SCF E3 ubiquitin ligase. In this study, we identified a novel murine F-box/WD40 repeat-containing protein, mHOS (a homologue of HOS/βTrCP2). mHOS efficiently binds Skp1 protein (a ‘core’ component of SCF ubiquitin ligase), and phosphorylated IκBα. We found that mHOS associates with SCF-ROC1 E3 ubiquitin ligase activity. We have also observed that mHOS is overexpressed in chemically-induced mouse skin tumors, and its overexpression (but not accelerated IκB phosphorylation) coincides with the accelerated degradation of IκB in vivo. The role of mHOS in the constitutive activation of NF-κB in skin carcinogenesis is discussed.

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References

  • Baeuerle PA, Baichwal VR . 1997 Adv. Immunol. 65: 111–137

  • Baichwal VR, Baeuerle PA . 1997 Curr. Biol. 7: R94–96

  • Barnes PJ, Karin M . 1997 N. Engl. J. Med. 336: 1066–1071

  • Budunova IV, Perez P, Vaden VR, Spiegelman VS, Slaga TJ, Jorcano JL . 1999 Oncogene 18: 7423–7431

  • Deshaies RJ . 1999 Annu. Rev. Cell Dev. Biol. 15: 435–467

  • DiGiovanni J, Beltran L, Rupp A, Harvey RG, Gill RD . 1993 Mol. Carcinog. 8: 272–279

  • Finco TS, Westwick JK, Norris JL, Beg AA, Der CJ, Baldwin Jr AS . 1997 J. Biol. Chem. 272: 24113–24116

  • Fuchs SY, Chen A, Xiong Y, Pan ZQ, Ronai Z . 1999 Oncogene 18: 2039–2046

  • Hart M, Concordet JP, Lassot I, Albert I, del los Santos R, Durand H, Perret C, Rubinfeld B, Margottin F, Benarous R, Polakis P . 1999 Curr. Biol. 9: 207–210

  • Hatakeyama S, Kitagawa M, Nakayama K, Shirane M, Matsumoto M, Hattori K, Higashi H, Nakano H, Okumura K, Onoe K, Good RA, Nakayama K . 1999 Proc. Natl. Acad. Sci. USA 96: 3859–3863

  • Jiang J, Struhl G . 1998 Nature 391: 493–496

  • Jo H, Zhang R, Zhang H, McKinsey TA, Shao J, Beauchamp RD, Ballard DW, Liang P . 2000 Oncogene 19: 841–849

  • Kitagawa M, Hatgakeyama S, Shirane M, Matsumoto M, Ishida N, Hattori K, Nakamichi I, Kikuchi A, Nakayama K . 1999 EMBO J. 18: 2401–2410

  • Kroll M, Margottin F, Kohl A, Renard P, Durand H, Concordet JP, Bachelerie F, Arenzana-Seisdedos F, Benarous R . 1999 J. Biol. Chem. 274: 7941–7945

  • LaCasse EC, Baird S, Korneluk RG, MacKenzie AE . 1998 Oncogene 17: 3247–3259

  • Latres E, Chiaur DS, Pagano M . 1999 Oncogene 18: 849–854

  • Liu C, Kato Y, Zhang Z, Do VM, Yankner BA, He X . 1999 Proc. Natl. Acad. Sci. USA 96: 6273–6278

  • Margottin F, Bour SP, Durand H, Selig L, Benichou S, Richard V, Thomas D, Strebel K, Benarous R . 1998 Mol. Cell 1: 565–574

  • Mayo MW, Wang CY, Cogswell PC, Rogers-Graham KS, Lowe SW, Der CJ, Baldwin Jr AS . 1997 Science 278: 1812–1815

  • Pelling JC, Ernst SM, Strawhecker JM, Johnson JA, Nairn RS, Slaga TJ . 1986 Carcinogenesis 7: 1599–1602

  • Pelling JC, Fischer SM, Neades R, Strawhecker J, Schweickert L . 1987 Carcinogenesis 8: 1481–1484

  • Pelling JC, Neades R, Strawhecker J . 1988 Carcinogenesis 9: 665–667

  • Rodriguez-Puebla ML, LaCava M, Bolontrade MF, Russell J, Conti CJ . 1999 Mol. Carcinog. 26: 150–156

  • Siebenlist U, Franzoso G, Brown K . 1994 Annu. Rev. Cell Biol. 10: 405–455

  • Soldatenkov VA, Dritschilo A, Ronai Z, Fuchs SY . 1999 Cancer Res. 59: 5085–5088

  • Sonenshein GE . 1997 Semin. Cancer Biol. 8: 113–119

  • Spencer E, Jiang J, Chen ZJ . 1999 Genes Dev. 13: 284–294

  • Spiegelman VS, Slaga TJ, Pagano M, Minamoto T, Ronai Z, Fuchs SY . 2000 Mol. Cell 5: 877–882

  • Spiegelman VS, Stavropoulos P, Latres E, Pagano M, Ronai Z, Slaga TJ, Fuchs SY . 2001 J. Biol. Chem. 276: 27152–27158

  • Suzuki H, Kobayashi M, Takeuchi M, Furuichi K, Chiba T, Tanaka K . 1999 FEBS Lett. 458: 343–348

  • Tan P, Fuchs SY, Chen A, Wu K, Gomez C, Ronai Z, Pan ZQ . 1999 Mol. Cell 3: 527–533

  • Verma IM, Stevenson J . 1997 Proc. Natl. Acad. Sci. USA 94: 11758–11760

  • Winston JT, Strack P, Beer-Romero P, Chu CY, Elledge SJ, Harper JW . 1999 Genes Dev. 13: 270–283

  • Wu K, Fuchs SY, Chen A, Tan P, Gomez C, Ronai Z, Pan ZQ . 2000 Mol. Cell Biol. 20: 1382–1393

  • Xu Y, Bialik S, Jones BE, Iimuro Y, Kitsis RN, Srinivasan A, Brenner DA, Czaja MJ . 1998 Am. J. Physiol. 275: C1058–1066

  • Yaron A, Gonen H, Alkalay I, Hatzubai A, Jung S, Beyth S, Mercurio F, Manning AM, Ciechanover A, Ben-Neriah Y . 1997 EMBO J. 16: 6486–6494

  • Yaron A, Hatzubai A, Davis M, Lavon I, Amit S, Manning AM, Andersen JS, Mann M, Mercurio F, Ben-Neriah Y . 1998 Nature 396: 590–594

  • Zhang XY, Safah H, Mudad R, Maher E, Krause J, Miller A, Ehrlich M . 1997 Am. J. Hematol. 55: 205–207

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Acknowledgements

We thank Drs V Fried, D Ballard, R Deshaies, and M Karin, for their generous gifts of reagents. We thank Dr R Strange for the critical suggestions and Dr K Spiegelman for help with the manuscript preparation. The study was supported by NIH grants CA 76262 (to TJ Slaga) and CA 92900 (to SY Fuchs).

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Authors and Affiliations

  1. AMC Cancer Research Center, Lakewood, 80214, Colorado, CO, USA

    Neehar Bhatia, Thomas J Slaga & Vladimir S Spiegelman

  2. Department of Animal Biology, University of Pennsylvania, Philadelphia, 19104, Pennsylvania PA, USA

    Jason R Herter & Serge Y Fuchs

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  1. Neehar Bhatia
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  2. Jason R Herter
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  3. Thomas J Slaga
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  4. Serge Y Fuchs
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  5. Vladimir S Spiegelman
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Corresponding author

Correspondence to Vladimir S Spiegelman.

Additional information

The coding sequence of mHOS has been deposited in GenBank database (accession number AY038079).

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Bhatia, N., Herter, J., Slaga, T. et al. Mouse homologue of HOS (mHOS) is overexpressed in skin tumors and implicated in constitutive activation of NF-κB. Oncogene 21, 1501–1509 (2002). https://doi.org/10.1038/sj.onc.1205311

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