Blood Journal
Leading the way in experimental and clinical research in hematology

Nur77 converts phenotype of Bcl-B, an antiapoptotic protein expressed in plasma cells and myeloma

  1. Frederic Luciano1,
  2. Maryla Krajewska1,
  3. Paulina Ortiz-Rubio1,
  4. Stan Krajewski1,
  5. Dayong Zhai1,
  6. Benjamin Faustin1,
  7. Jean-Marie Bruey1,
  8. Beatrice Bailly-Maitre1,
  9. Alan Lichtenstein2,
  10. Siva Kumar Kolluri1,
  11. Arnold C. Satterthwait1,
  12. Xiao-Kun Zhang1, and
  13. John C. Reed1
  1. 1Burnham Institute for Medical Research, La Jolla, CA;
  2. 2Veterans Administration Greater Los Angeles Healthcare System, CA
This article has an Erratum 113(7):1613

Abstract

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.

  • Submitted November 9, 2006.
  • Accepted December 18, 2006.
View Full Text