Broad degradation of proapoptotic proteins with the conserved Bcl-2 homology domain 3 during infection with Chlamydia trachomatis.
Chlamydiae are obligate intracellular bacteria that can inhibit apoptosis of their host cell. As shown recently, this inhibition is in part explained by the proteolytic degradation of the proapoptotic Bcl-2 family members (BH3-only proteins) Bim, Puma, and Bad upon chlamydial infection. In this study, we further explore this antiapoptotic mechanism. In cells infected with a Chlamydia trachomatis L2 strain, Bim, Puma, and Bad were degraded with similar kinetics, and the degradation of all three was blocked by inhibition of the proteasome. Furthermore, the BH3-only proteins Bmf, Noxa, and tBid were also targeted by chlamydial infection. The constitutively expressed Bmf disappeared during infection. When Noxa was experimentally induced, the levels were also reduced by infection with C. trachomatis. In death-receptor-induced apoptosis, cleaved and activated tBid was degraded, and this destruction was also prevented by inhibition of the proteasome. These results show that chlamydial infection leads to a broad degradation of BH3-only proteins. This loss of proapoptotic factors can explain the almost general protection of infected cells against apoptotic stimuli.
Ying
Songmin
S
Institute for Medical Microbiology, Technische Universität München, Trogerstr. 9, D-81675 Munich, Germany.
Seiffert
Barbara M
BM
Häcker
Georg
G
Fischer
Silke F
SF
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D051023:BH3 Interacting Domain Death Agonist Protein; D000072224:Bcl-2-Like Protein 11; D002352:Carrier Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D002692:Chlamydia trachomatis / Q000472:pathogenicity*; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D008565:Membrane Proteins / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000737:chemistry / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051025:bcl-Associated Death Protein
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C494819:BAD protein, human; C438378:BBC3 protein, human; C000606775:BCL2L11 protein, human; D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; C486655:BMF protein, human; D000072224:Bcl-2-Like Protein 11; D002352:Carrier Proteins; D008565:Membrane Proteins; C498702:PMAIP1 protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051025:bcl-Associated Death Protein
Science. 1999 Nov 26;286(5445):1735-8
10576740
Nature. 1999 Aug 26;400(6747):886-91
10476969
Infect Immun. 2001 Nov;69(11):7121-9
11598088
Infect Immun. 2002 Jan;70(1):55-61
11748163
J Cell Sci. 2002 Apr 15;115(Pt 8):1567-74
11950875
FEMS Microbiol Lett. 2002 May 21;211(1):1-6
12052542
Immunity. 2002 Jun;16(6):759-67
12121658
J Biol Chem. 2002 Aug 2;277(31):27912-8
12023951
Nature. 2003 Aug 21;424(6951):952-6
12931191
Science. 2003 Nov 7;302(5647):1036-8
14500851
Infect Immun. 2004 Jan;72(1):451-60
14688126
Infect Immun. 2004 Feb;72(2):1107-15
14742558
Infect Immun. 2004 Sep;72(9):5470-4
15322047
Nat Rev Microbiol. 2004 Oct;2(10):802-8
15378044
J Exp Med. 2004 Oct 4;200(7):905-16
15452181
J Infect Dis. 1975 Jul;132(1):87-105
1097546
Cell. 1994 Mar 11;76(5):777-9
8124715
J Exp Med. 1998 Feb 16;187(4):487-96
9463399
EMBO J. 1998 Mar 16;17(6):1675-87
9501089
Cell. 1998 Aug 21;94(4):481-90
9727491
Cell. 1998 Aug 21;94(4):491-501
9727492
Hum Gene Ther. 1998 Sep 1;9(13):1939-50
9741432
Cell. 1999 Mar 5;96(5):625-34
10089878
Infect Immun. 2000 Apr;68(4):2237-44
10722625