This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Chang, C. C.
Right arrow Articles by Dalla-Favera, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chang, C. C.
Right arrow Articles by Dalla-Favera, R.

 Previous Article  |  Next Article 

Mol. Cell. Biol., 09 1995, 5180-5187, Vol 15, No. 9
Copyright © 1995, American Society for Microbiology

Rearranged NFKB-2 genes in lymphoid neoplasms code for constitutively active nuclear transactivators

CC Chang, J Zhang, L Lombardi, A Neri and R Dalla-Favera
Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.

The NFKB-2 gene codes for an NF-kappa B-related transcription factor containing rel-polyG-ankyrin domains. Chromosomal rearrangements of the NFKB-2 locus have been found in various types of lymphoid neoplasms, suggesting that they may contribute to lymphomagenesis. Rearrangements cluster within the 3'-terminal ankyrin-encoding domain of the NFKB-2 gene and lead to the production of C-terminally truncated proteins which, in some cases, are fused to heterologous protein domains. In order to determine the functional consequences of these alterations, we have analyzed the subcellular localization, DNA binding, and transcriptional activity of two representative tumor-associated mutants in which the ankyrin domain is either terminally truncated (NFKB-2p85) or truncated and joined to an out-of-frame immunoglobulin C alpha domain (lyt-10C alpha). Immunofluorescence studies performed on cells transfected with p85 or lyt-10C alpha expression vectors showed that both the abnormal proteins were constitutively localized in the nucleus. Immunoprecipitation analysis of UV-cross-linked DNA-protein adducts showed that p85 can bind kappa B sites in its unprocessed form. Cotransfection of p85 or lyt-10C alpha expression vectors with kappa B- driven reporter plasmids showed that both p85 and lyt-10C alpha have retained the ability to mediate transcriptional activation via heterodimerization with Rel-Ap65 but have lost the transrepression activity associated with homodimeric DNA binding. Furthermore, both p85 and lyt-10C alpha were capable of independent transactivation of kappa B-reporter genes and this activity could not be further stimulated by Bcl-3.(ABSTRACT TRUNCATED AT 250 WORDS)


This article has been cited by other articles:

  • Wang, Z., Zhang, B., Yang, L., Ding, J., Ding, H.-F. (2008). Constitutive Production of NF-{kappa}B2 p52 Is Not Tumorigenic but Predisposes Mice to Inflammatory Autoimmune Disease by Repressing Bim Expression. J. Biol. Chem. 283: 10698-10706 [Abstract] [Full Text]  
  • Zhang, B., Wang, Z., Li, T., Tsitsikov, E. N., Ding, H.-F. (2007). NF-{kappa}B2 mutation targets TRAF1 to induce lymphomagenesis. Blood 110: 743-751 [Abstract] [Full Text]  
  • Hammerman, P. S., Fox, C. J., Cinalli, R. M., Xu, A., Wagner, J. D., Lindsten, T., Thompson, C. B. (2004). Lymphocyte Transformation by Pim-2 Is Dependent on Nuclear Factor-{kappa}B Activation. Cancer Res. 64: 8341-8348 [Abstract] [Full Text]  
  • Pasqualucci, L., Migliazza, A., Basso, K., Houldsworth, J., Chaganti, R. S. K., Dalla-Favera, R. (2003). Mutations of the BCL6 proto-oncogene disrupt its negative autoregulation in diffuse large B-cell lymphoma. Blood 101: 2914-2923 [Abstract] [Full Text]  
  • Caamano, J., Hunter, C. A. (2002). NF-{kappa}B Family of Transcription Factors: Central Regulators of Innate and Adaptive Immune Functions. Clin. Microbiol. Rev. 15: 414-429 [Abstract] [Full Text]  
  • Davis, R. E., Brown, K. D., Siebenlist, U., Staudt, L. M. (2001). Constitutive Nuclear Factor {kappa}B Activity Is Required for Survival of Activated B Cell-like Diffuse Large B Cell Lymphoma Cells. JEM 194: 1861-1874 [Abstract] [Full Text]  
  • Willis, T. G., Dyer, M. J. S. (2000). The role of immunoglobulin translocations in the pathogenesis of B-cell malignancies. Blood 96: 808-822 [Full Text]  
  • Harris, M. B., Chang, C.-C., Berton, M. T., Danial, N. N., Zhang, J., Kuehner, D., Ye, B. H., Kvatyuk, M., Pandolfi, P. P., Cattoretti, G., Dalla-Favera, R., Rothman, P. B. (1999). Transcriptional Repression of Stat6-Dependent Interleukin-4-Induced Genes by BCL-6: Specific Regulation of Ivarepsilon Transcription and Immunoglobulin E Switching. Mol. Cell. Biol. 19: 7264-7275 [Abstract] [Full Text]  
  • Sachdev, S., Hannink, M. (1998). Loss of Ikappa Balpha -Mediated Control over Nuclear Import and DNA Binding Enables Oncogenic Activation of c-Rel. Mol. Cell. Biol. 18: 5445-5456 [Abstract] [Full Text]  
  • Carrasco, D., Cheng, J., Lewin, A., Warr, G., Yang, H., Rizzo, C., Rosas, F., Snapper, C., Bravo, R. (1998). Multiple Hemopoietic Defects and Lymphoid Hyperplasia in Mice Lacking the Transcriptional Activation Domain of the c-Rel Protein. JEM 187: 973-984 [Abstract] [Full Text]  
  • Caamano, J. H., Rizzo, C. A., Durham, S. K., Barton, D. S., Raventos-Suarez, C., Snapper, C. M., Bravo, R. (1998). Nuclear Factor (NF)-{kappa}B2 (p100/p52) Is Required for Normal Splenic Microarchitecture and B Cell-mediated Immune Responses. JEM 187: 185-196 [Abstract] [Full Text]  
  • Ishikawa, H., Carrasco, D., Claudio, E., Ryseck, R.-P., Bravo, R. (1997). Gastric Hyperplasia and Increased Proliferative Responses of Lymphocytes in Mice Lacking the COOH-terminal Ankyrin Domain of NF-{kappa}B2. JEM 186: 999-1014 [Abstract] [Full Text]  
  • Carrasco, D., Perez, P., Lewin, A., Bravo, R. (1997). I{kappa}B{alpha} Overexpression Delays Tumor Formation in v-rel Transgenic Mice. JEM 186: 279-288 [Abstract] [Full Text]  
  • Raziuddin, A., Court, D., Sarkar, F. H., Liu, Y.-L., Kung, H.-f., Raziuddin, R. (1997). A c-erbB-2 Promoter-specific Nuclear Matrix Protein from Human Breast Tumor Tissues Mediates NF-kappa B DNA Binding Activity. J. Biol. Chem. 272: 15715-15720 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»