|
Originally published In Press as doi:10.1074/jbc.M602796200 on August 28, 2006
J. Biol. Chem., Vol. 281, Issue 42, 31495-31501, October 20, 2006
The Secreted Protease Factor CPAF Is Responsible for Degrading Pro-apoptotic BH3-only Proteins in Chlamydia trachomatis-infected Cells*
Mustak Pirbhai ,
Feng Dong ,
Youmin Zhong ,
Kelvin Z. Pan , and
Guangming Zhong 1
From the
Department of Microbiology and Immunology, University of Texas Health Science Center, San Antonio, Texas 78229 and the Department of Microbiology and Immunology, Medical College of Ohio, Toledo, Ohio 43614
Chlamydia trachomatis has evolved a profound anti-apoptotic activity that may aid in chlamydial evasion of host defense. The C. trachomatis anti-apoptotic activity has been correlated with blockade of mitochondrial cytochrome c release, inhibition of Bax and Bak activation, and degradation of BH3-only proteins. This study presents evidence that a chlamydia-secreted protease factor designated CPAF is both necessary and sufficient for degrading the BH3-only proteins. When the C. trachomatis-infected cell cytosolic extracts were fractionated by column chromatography, both the CPAF protein and activity elution peaks overlapped with the BH3-only protein degradation activity peak. Depletion of CPAF with a CPAF-specific antibody removed the BH3-only protein degradation activity from the infected cell cytosolic extracts, whereas depletion with control antibodies failed to do so. Notably, recombinant CPAF expressed in bacteria was able to degrade the BH3-only proteins, whereas CPAF mutants similarly prepared from bacteria failed to do so. Finally, bacterium-expressed CPAF also degraded the human BH3-only protein Puma purified from bacteria. These results demonstrate that CPAF contributes to the chlamydial anti-apoptotic activity by degrading the pro-apoptotic BH3-only Bcl-2 subfamily members.
Received for publication, March 24, 2006
, and in revised form, August 21, 2006.
* This work was supported in part by National Institutes of Health Grants R01 AI57450, R01 AI64537, and R01 AI47997 (to G. Z.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 To whom correspondence should be addressed: Dept. of Microbiology and Immunology, University of Texas Health Science Center, 7703 Floyd Curl Dr., San Antonio, TX 78229. Tel.: 210-567-1169; Fax: 210-567-0293; E-mail: Zhongg{at}uthscsa.edu.

CiteULike Complore Connotea Del.icio.us Digg Reddit Technorati What's this?
This article has been cited by other articles:

|
 |

|
 |
 
A. DiFeo, F. Huang, J. Sangodkar, E. A. Terzo, D. Leake, G. Narla, and J. A. Martignetti
KLF6-SV1 Is a Novel Antiapoptotic Protein That Targets the BH3-Only Protein NOXA for Degradation and Whose Inhibition Extends Survival in an Ovarian Cancer Model
Cancer Res.,
June 1, 2009;
69(11):
4733 - 4741.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. A. Paschen, J. G. Christian, J. Vier, F. Schmidt, A. Walch, D. M. Ojcius, and G. Hacker
Cytopathicity of Chlamydia is largely reproduced by expression of a single chlamydial protease
J. Cell Biol.,
October 23, 2008;
182(1):
117 - 127.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
I. Jorgensen and R. H. Valdivia
Pmp-Like Proteins Pls1 and Pls2 Are Secreted into the Lumen of the Chlamydia trachomatis Inclusion
Infect. Immun.,
September 1, 2008;
76(9):
3940 - 3950.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Z. Li, D. Chen, Y. Zhong, S. Wang, and G. Zhong
The Chlamydial Plasmid-Encoded Protein pgp3 Is Secreted into the Cytosol of Chlamydia-Infected Cells
Infect. Immun.,
August 1, 2008;
76(8):
3415 - 3428.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
X. Jiang, C. Shen, J. Rey-Ladino, H. Yu, and R. C. Brunham
Characterization of Murine Dendritic Cell Line JAWS II and Primary Bone Marrow-Derived Dendritic Cells in Chlamydia muridarum Antigen Presentation and Induction of Protective Immunity
Infect. Immun.,
June 1, 2008;
76(6):
2392 - 2401.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
H. L. Howie, S. L. Shiflett, and M. So
Extracellular Signal-Regulated Kinase Activation by Neisseria gonorrhoeae Downregulates Epithelial Cell Proapoptotic Proteins Bad and Bim
Infect. Immun.,
June 1, 2008;
76(6):
2715 - 2721.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. Sun, J. Kintner, and R. V. Schoborg
The host adherens junction molecule nectin-1 is downregulated in Chlamydia trachomatis-infected genital epithelial cells
Microbiology,
May 1, 2008;
154(5):
1290 - 1299.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. L. Johnson, C. B. Stone, and J. B. Mahony
Interactions between CdsD, CdsQ, and CdsL, Three Putative Chlamydophila pneumoniae Type III Secretion Proteins
J. Bacteriol.,
April 15, 2008;
190(8):
2972 - 2980.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. E. Voth, D. Howe, and R. A. Heinzen
Coxiella burnetii Inhibits Apoptosis in Human THP-1 Cells and Monkey Primary Alveolar Macrophages
Infect. Immun.,
September 1, 2007;
75(9):
4263 - 4271.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. Hermann
Review: Variability of host pathogen interaction
Innate Immunity,
August 1, 2007;
13(4):
199 - 218.
[Abstract]
[PDF]
|
 |
|

|
 |

|
 |
 
A. G. Miraglia, S. Travaglione, S. Meschini, L. Falzano, P. Matarrese, M. G. Quaranta, M. Viora, C. Fiorentini, and A. Fabbri
Cytotoxic Necrotizing Factor 1 Prevents Apoptosis via the Akt/I{kappa}B Kinase Pathway: Role of Nuclear Factor-{kappa}B and Bcl-2
Mol. Biol. Cell,
July 1, 2007;
18(7):
2735 - 2744.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. P. Lad, J. Li, J. da Silva Correia, Q. Pan, S. Gadwal, R. J. Ulevitch, and E. Li
Cleavage of p65/RelA of the NF-{kappa}B pathway by Chlamydia
PNAS,
February 20, 2007;
104(8):
2933 - 2938.
[Abstract]
[Full Text]
[PDF]
|
 |
|
Copyright © 2006 by the American Society for Biochemistry and Molecular Biology.
|
Advertisement
Advertisement
|