|
|
Blood, 1 August 2006, Vol. 108, No. 3, pp. 821-829.
Prepublished online as a Blood First Edition Paper on April 11, 2006; DOI 10.1182/blood-2005-11-006817.
 Previous Article | Next Article 
Submitted November 30, 2005
Accepted March 11, 2006
RAX, the PKR activator, sensitizes cells to inflammatory
cytokines, serum withdrawal, chemotherapy and viral
infection
Richard L Bennett, William L Blalock, Dean M Abtahi, Yu Pan, Sue A Moyer, and W Stratford May*
University of Florida, Shands Cancer Center
Department of Immunology and Molecular Genetics, University of Florida
* Corresponding author; email: smay{at}ufscc.ufl.edu.
While the interferon-inducible dsRNA-dependent protein
kinase PKR is reported to initiate apoptosis in some
instances, the mechanism by which diverse stress stimuli
activate PKR remains unknown. Now we report that RAX,
the only known cellular activator for PKR, initiates PKR
activation in response to a broad range of stresses
including serum deprivation, cytotoxic cytokine or
chemotherapy treatment or viral infection. Thus, knock-
down of RAX expression by 80% using siRNA prevents IFN /TNF -induced PKR activation and eIF2 phosphorylation, I B degradation, IRF-1
expression and STAT1 phosphorylation, resulting in
enhanced MEF cell survival. In contrast, expression of
exogenous RAX, but not of the nonphosphorylatable,
dominant-negative RAX(S18A) mutant, sensitizes cells to
IFN/TNF, mitomycin C, or serum
deprivation in association with increased PKR activity
and apoptosis. Furthermore, RAX(S18A) expression in
Fanconi anemia complementation group C null MEF cells
not only prevents PKR activation but also blocks
hypersensitivity to IFN/TNF or mitomycin
C that results in enhanced apoptosis. In addition,
reduced RAX expression facilitates productive viral
infection with VSV and promotes anchorage-independent
colony growth of MEF cells. Collectively these data
indicate that RAX may function as a negative regulator
of growth that is required to activate PKR in response
to a broad range of apoptosis-inducing stress.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
K. H. Kok, M.-H. J. Ng, Y.-P. Ching, and D.-Y. Jin
Human TRBP and PACT Directly Interact with Each Other and Associate with Dicer to Facilitate the Production of Small Interfering RNA
J. Biol. Chem.,
June 15, 2007;
282(24):
17649 - 17657.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Yang, S. Wu, X. Su, and W. S. May
JAZ mediates G1 cell-cycle arrest and apoptosis by positively regulating p53 transcriptional activity
Blood,
December 15, 2006;
108(13):
4136 - 4145.
[Abstract]
[Full Text]
[PDF]
|
|
|
| |
