| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 278, Issue 14, 12294-12304, April 4, 2003
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Departments of The promyelocytic leukemia protein (PML) is a
growth/tumor suppressor essential for induction of apoptosis by
diverse apoptotic stimuli. The mechanism by which PML regulates cell
death remains unclear. In this study we found that ectopic expression
of PML potentiates cell death by apoptosis in the tumor necrosis factor
Promyelocytic Leukemia Protein Sensitizes Tumor
Necrosis Factor
-Induced Apoptosis by Inhibiting the NF-
B
Survival Pathway*
,,
Molecular Pathology and
§ Clinical Investigation, the University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030 and the
¶ Department of Human Genetics, Memorial Sloan-Kettering Cancer
Center, New York, New York 10021
(TNF)-resistant cell line U2OS and other cell lines. Treatment with TNF significantly sensitized these cells to apoptosis in a
p53-independent manner. PML/TNF-induced cell death is associated with DNA fragmentation, activation of caspase-3, -7, and -8, and degradation of DNA fragmentation factor/inhibitor of CAD.
PML/TNF-induced cell death could be blocked by the caspase-8
inhibitors CrmA and c-FLIP but not by Bcl-2. These findings indicate
that this cell death event is initiated through the death
receptor-dependent apoptosis pathway. PML is a
transcriptional repressor of NF-
B by interacting with RelA/p65 and
prevents its binding to the cognate enhancer through the C terminus.
Coimmunoprecipitation and double-color immunofluorescence staining
demonstrated that PML physically interacts with RelA/p65 in
vivo and the two proteins colocalized at the endogenous levels.
Overexpression of NF-B rescued cell death induced by PML/TNF.
Furthermore, PML
/ mouse embryo fibroblasts are more
resistant to TNF-induced apoptosis. Together this study defines
a novel mechanism by which PML induces apoptosis through repression of
the NF-B survival pathway.
*
This work was supported by Grant CA 55577 from the National
Institutes of Health (to K.-S. C.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Dept. of Molecular
Pathology, the University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Unit 89, Houston, TX 77030. Tel.:
713-792-2581; Fax: 713-794-4672; E-mail:
kchang@mail.mdanderson.org.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  Y.-H. Choi, R. Bernardi, P. P. Pandolfi, and E. N. Benveniste The promyelocytic leukemia protein functions as a negative regulator of IFN-{gamma} signaling PNAS, December 5, 2006; 103(49): 18715 - 18720. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-T. Huang, S.-L. Pan, J.-H. Guh, Y.-L. Chang, F.-Y. Lee, S.-C. Kuo, and C.-M. Teng YC-1 suppresses constitutive nuclear factor-{kappa}B activation and induces apoptosis in human prostate cancer cells Mol. Cancer Ther., October 1, 2005; 4(10): 1628 - 1635. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Cheng, C. Cenciarelli, G. Nelkin, R. Tsan, D. Fan, C. Cheng-Mayer, and I. J. Fidler Molecular Mechanism of hTid-1, the Human Homolog of Drosophila Tumor Suppressor l(2)Tid, in the Regulation of NF-{kappa}B Activity and Suppression of Tumor Growth Mol. Cell. Biol., January 1, 2005; 25(1): 44 - 59. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Shin, B. Park, S. Cho, S. Lee, Y. Kim, S.-O. Lee, K. Cho, S. Lee, B.-S. Jin, J.-H. Ahn, et al. Promyelocytic Leukemia Is a Direct Inhibitor of SAPK2/p38 Mitogen-activated Protein Kinase J. Biol. Chem., September 24, 2004; 279(39): 40994 - 41003. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Banno, A. Gazel, and M. Blumenberg Effects of Tumor Necrosis Factor-{alpha} (TNF{alpha}) in Epidermal Keratinocytes Revealed Using Global Transcriptional Profiling J. Biol. Chem., July 30, 2004; 279(31): 32633 - 32642. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-Y. Park, H. D. Jang, S. Y. Lee, K.-J. Lee, and E. Kim Fas-associated Factor-1 Inhibits Nuclear Factor-{kappa}B (NF-{kappa}B) Activity by Interfering with Nuclear Translocation of the RelA (p65) Subunit of NF-{kappa}B J. Biol. Chem., January 23, 2004; 279(4): 2544 - 2549. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z.-X. Xu, R.-X. Zhao, T. Ding, T. T. Tran, W. Zhang, P. P. Pandolfi, and K.-S. Chang Promyelocytic Leukemia Protein 4 Induces Apoptosis by Inhibition of Survivin Expression J. Biol. Chem., January 16, 2004; 279(3): 1838 - 1844. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
