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Blood, 1 May 2007, Vol. 109, No. 9, pp. 3849-3855. Prepublished online as a Blood First Edition Paper on February 13, 2007; DOI 10.1182/blood-2006-11-056879. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2006-11-056879v1 blood-2006-11-056879v2 109/9/3849    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Luciano, F. Articles by Reed, J. C. Search for Related Content PubMed PubMed Citation Articles by Luciano, F. Articles by Reed, J. C. Related Collections Immunobiology Neoplasia Apoptosis Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Nur77 converts phenotype of Bcl-B, an antiapoptotic protein expressed in plasma cells and myeloma Frederic Luciano1, Maryla Krajewska1, Paulina Ortiz-Rubio1, Stan Krajewski1, Dayong Zhai1, Benjamin Faustin1, Jean-Marie Bruey1, Beatrice Bailly-Maitre1, Alan Lichtenstein2, Siva Kumar Kolluri1, Arnold C. Satterthwait1, Xiao-Kun Zhang1, and John C. Reed1 1 Burnham Institute for Medical Research, La Jolla, CA; 2 Veterans Administration Greater Los Angeles Healthcare System, CA Defects in apoptosis mechanisms play important roles in malignancy and autoimmunity. Orphan nuclear receptor Nur77/TR3 has been demonstrated to bind antiapoptotic protein Bcl-2 and convert it from a cytoprotective to a cytodestructive protein, representing a phenotypic conversion mechanism. Of the 6 antiapoptotic human Bcl-2 family members, we found that Nur77/TR3 binds strongest to Bcl-B, showing selective reactivity with Bcl-B, Bcl-2, and Bfl-1 but not Bcl-XL, Mcl-1, or Bcl-W. Nur77 converts the phenotype of Bcl-B from antiapoptotic to proapoptotic. Bcl-B is prominently expressed in plasma cells and multiple myeloma. Endogenous Bcl-B associates with endogenous Nur77 in RPMI 8226 myeloma cells, where RNA interference experiments demonstrated dependence on Bcl-B for Nur77-induced apoptosis. Furthermore, a Nur77-mimicking peptide killed RPMI 8226 myeloma cells through a Bcl-B–dependent mechanism. Because Bcl-B is abundantly expressed in plasma cells and some myelomas, these findings raise the possibility of exploiting the Nur77/Bcl-B mechanism for apoptosis for eradication of autoimmune plasma cells or myeloma. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Bcl-B and Nur77/TR3: a deadly combination Dharminder Chauhan and Kenneth C. Anderson Blood 2007 109: 3622. [Full Text] [PDF] This article has been cited by other articles: M. Krajewska, S. Kitada, J. N. Winter, D. Variakojis, A. Lichtenstein, D. Zhai, M. Cuddy, X. Huang, F. Luciano, C. H. Baker, et al. Bcl-B Expression in Human Epithelial and Nonepithelial Malignancies Clin. Cancer Res., May 15, 2008; 14(10): 3011 - 3021. [Abstract] [Full Text] [PDF] D. Zhai, C. Jin, Z. Huang, A. C. Satterthwait, and J. C. Reed Differential Regulation of Bax and Bak by Anti-apoptotic Bcl-2 Family Proteins Bcl-B and Mcl-1 J. Biol. Chem., April 11, 2008; 283(15): 9580 - 9586. [Abstract] [Full Text] [PDF] J. C. Reed Bcl-2-family proteins and hematologic malignancies: history and future prospects Blood, April 1, 2008; 111(7): 3322 - 3330. [Abstract] [Full Text] [PDF]

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