|
|
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.
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-Bdependent 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:

|
 |

|
 |
 
S. Maddika, S. Panigrahi, E. Wiechec, S. Wesselborg, U. Fischer, K. Schulze-Osthoff, and M. Los
Unscheduled Akt-Triggered Activation of Cyclin-Dependent Kinase 2 as a Key Effector Mechanism of Apoptin's Anticancer Toxicity
Mol. Cell. Biol.,
March 1, 2009;
29(5):
1235 - 1248.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. W. Yip, P. H.C. Godoi, D. Zhai, X. Garcia, J. F. Cellitti, M. Cuddy, M. Gerlic, Y. Chen, A. Satterthwait, S. Vasile, et al.
A TR3/Nur77 Peptide-Based High-Throughput Fluorescence Polarization Screen for Small Molecule Bcl-B Inhibitors
J Biomol Screen,
August 1, 2008;
13(7):
665 - 673.
[Abstract]
[PDF]
|
 |
|

|
 |

|
 |
 
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]
|
 |
|
|
|