[en] The oncogenic protein BCL-3 activates or represses gene transcription through binding with the NF-kappaB proteins p50 and p52 and is degraded through a phospho- and GSK3-dependent pathway. However, the mechanisms underlying its degradation remain poorly understood. Yeast-two-hybrid analysis led to the identification of the proteasome subunit PSMB1 as a BCL-3-associated protein. The binding of BCL-3 to PSMB1 is required for its degradation through the proteasome. Indeed, PSMB1-depleted cells are defective in degrading polyubiquitinated BCL-3. The N-terminal part of BCL-3 includes lysines 13 and 26 required for the K48-linked polyubiquitination of BCL-3. Moreover, the E3 ligase FBW7 known to polyubiquitinate a variety of substrates phosphorylated by GSK3 is dispensable for BCL-3 degradation. Thus, our data defined an unique motif of BCL-3 that is needed for its recruitment to the proteasome and identified PSMB1 as a key protein required for the proteasome-mediated degradation of a nuclear and oncogenic IkappaB protein.
Research center :
Giga-Signal Transduction - ULiège
Disciplines :
Laboratory medicine & medical technology Biochemistry, biophysics & molecular biology
Author, co-author :
Keutgens, Aurore ; Université de Liège - ULiège > Département de pharmacie > Département de pharmacie
Zhang-Shao, Xin ; Université de Liège - ULiège > Département de pharmacie > Chimie médicale
Shostak, Kateryna ; Université de Liège - ULiège > Département de pharmacie > Chimie médicale
Bours, V., Franzoso, G., Azarenko, V., Park, S., Kanno, T., Brown, K., and Siebenlist, U. (1993) Cell 72, 729-739
Palmer, S., and Chen, Y. H. (2008) Immunol. Res. 42, 210-218
Franzoso, G., Bours, V., Azarenko, V., Park, S., Tomita-Yamaguchi, M., Kanno, T., Brown, K., and Siebenlist, U. (1993) EMBO J. 12, 3893-3901
Kerr, L. D., Duckett, C. S., Wamsley, P., Zhang, Q., Chiao, P., Nabel, G., McKeithan, T. W., Baeuerle, P. A., and Verma, I. M. (1992) Genes Dev. 6(12A), 2352-2363
Nolan, G. P., Fujita, T., Bhatia, K., Huppi, C., Liou, H. C., Scott, M. L., and Baltimore, D. (1993) Mol. Cell. Biol. 13, 3557-3566
McKeithan, T. W., Rowley, J. D., Shows, T. B., and Diaz, M. O. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 9257-9260
Ohno, H., Takimoto, G., and McKeithan, T. W. (1990) Cell 60, 991-997
Karin, M., and Lin, A. (2002) Nat. Immunol. 3, 221-227
Mathas, S., Jöhrens, K., Joos, S., Lietz, A., Hummel, F., Janz, M., Jundt, F., Anagnostopoulos, I., Bommert, K., Lichter, P., Stein, H., Scheidereit, C., and Dörken, B. (2005) Blood 106, 4287-4293
Brenne, A. T., Fagerli, U. M., Shaughnessy, J. D., Jr., Våtsveen, T. K., Rø, T. B., Hella, H., Zhan, F., Barlogie, B., Sundan, A., Børset, M., and Waage, A. (2009) Eur. J. Haematol. 82, 354-363
Canoz, O., Rassidakis, G. Z., Admirand, J. H., and Medeiros, L. J. (2004) Mod. Pathol. 17, 911-917
Nishikori, M., Maesako, Y., Ueda, C., Kurata, M., Uchiyama, T., and Ohno, H. (2003) Blood 101, 2789-2796
Cogswell, P. C., Guttridge, D. C., Funkhouser, W. K., and Baldwin, A. S., Jr. (2000) Oncogene 19, 1123-1131
O'Neil, B. H., Bůzková, P., Farrah, H., Kashatus, D., Sanoff, H., Goldberg, R. M., Baldwin, A. S., and Funkhouser, W. K. (2007) Oncology 72, 97-104
Thornburg, N. J., Pathmanathan, R., and Raab-Traub, N. (2003) Cancer Res. 63, 8293-8301
Bignell, G. R., Warren, W., Seal, S., Takahashi, M., Rapley, E., Barfoot, R., Green, H., Brown, C., Biggs, P. J., Lakhani, S. R., Jones, C., Hansen, J., Blair, E., Hofmann, B., Siebert, R., Turner, G., Evans, D. G., Schrander-Stumpel, C., Beemer, F. A., van Den Ouweland, A., Halley, D., Delpech, B., Cleveland, M. G., Leigh, I., Leisti, J., and Rasmussen, S. (2000) Nat. Genet. 25, 160-165
Massoumi, R., Chmielarska, K., Hennecke, K., Pfeifer, A., and Fässler, R. (2006) Cell 125, 665-677
Viatour, P., Dejardin, E., Warnier, M., Lair, F., Claudio, E., Bureau, F., Marine, J. C., Merville, M. P., Maurer, U., Green, D., Piette, J., Siebenlist, U., Bours, V., and Chariot, A. (2004) Mol. Cell 16, 35-45
Ong, S. T., Hackbarth, M. L., Degenstein, L. C., Baunoch, D. A., Anastasi, J., and McKeithan, T. W. (1998) Oncogene 16, 2333-2343
Viatour, P., Legrand-Poels, S., van Lint, C., Warnier, M., Merville, M. P., Gielen, J., Piette, J., Bours, V., and Chariot, A. (2003) J. Biol. Chem. 278, 46541-46548
Gatot, J. S., Gioia, R., Chau, T. L., Patrascu, F., Warnier, M., Close, P., Chapelle, J. P., Muraille, E., Brown, K., Siebenlist, U., Piette, J., Dejardin, E., and Chariot, A. (2007) J. Biol. Chem. 282, 31131-31146
Robert, I., Aussems, M., Keutgens, A., Zhang, X., Hennuy, B., Viatour, P., Vanstraelen, G., Merville, M. P., Chapelle, J. P., de Leval, L., Lambert, F., Dejardin, E., Gothot, A., and Chariot, A. (2009) Oncogene 28, 1626-1638
Sachdev, S., Hoffmann, A., and Hannink, M. (1998) Mol. Cell. Biol. 18, 2524-2534
Brown, K., Gerstberger, S., Carlson, L., Franzoso, G., and Siebenlist, U. (1995) Science 267, 1485-1488
Wei, W., Jin, J., Schlisio, S., Harper, J. W., and Kaelin, W. G., Jr. (2005) Cancer Cell 8, 25-33
Welcker, M., Singer, J., Loeb, K. R., Grim, J., Bloecher, A., Gurien-West, M., Clurman, B. E., and Roberts, J. M. (2003) Mol. Cell 12, 381-392
Tetzlaff, M. T., Yu, W., Li, M., Zhang, P., Finegold, M., Mahon, K., Harper, J. W., Schwartz, R. J., and Elledge, S. J. (2004) Proc. Natl. Acad. Sci. U.S.A. 101, 3338-3345
Grim, J. E., Gustafson, M. P., Hirata, R. K., Hagar, A. C., Swanger, J., Welcker, M., Hwang, H. C., Ericsson, J., Russell, D. W., and Clurman, B. E. (2008) J. Cell Biol. 181, 913-920
Yaron, A., Hatzubai, A., Davis, M., Lavon, I., Amit, S., Manning, A. M., Andersen, J. S., Mann, M., Mercurio, F., and Ben-Neriah, Y. (1998) Nature 396, 590-594
Hanson, J. L., Hawke, N. A., Kashatus, D., and Baldwin, A. S. (2004) Cancer Res. 64, 7248-7255
Hanson, J. L., Anest, V., Reuther-Madrid, J., and Baldwin, A. S. (2003) J. Biol. Chem. 278, 34910-34917
Arsura, M., Mercurio, F., Oliver, A. L., Thorgeirsson, S. S., and Sonenshein, G. E. (2000) Mol. Cell. Biol. 20, 5381-5391
An, J., Mo, D., Liu, H., Veena, M. S., Srivatsan, E. S., Massoumi, R., and Rettig, M. B. (2008) Cancer Cell 14, 394-407
Minella, A. C., Welcker, M., and Clurman, B. E. (2005) Proc. Natl. Acad. Sci. U.S.A. 102, 9649-9654
Welcker, M., and Clurman, B. E. (2008) Nat. Rev. Cancer 8, 83-93