Abstract
TNFSF14/LIGHT is a member of the tumor necrosis factor superfamily that binds to lymphotoxin-β receptor (LTβR) to induce cell death via caspase-dependent and caspase-independent pathways. It has been shown that cellular inhibitor of apoptosis protein-1 inhibits cell death by binding to LTβR-TRAF2/TRAF3 complexes and caspases. In this study, we found that both Kaposi's sarcoma-associated herpesvirus K7 (KSHV-K7), a viral inhibitor of apoptosis protein, and the structurally related protein survivin-ΔEx3 could inhibit LTβR-mediated caspase-3 activation. However, only survivin-ΔEx3 could protect cells from LTβR-mediated cell death. The differential protective effects of survivin-ΔEx3 and KSHV-K7 can be attributed to the fact that survivin-ΔEx3, but not KSHV-K7, is able to maintain mitochondrial membrane potential and inhibit second mitochondria-derived activator of caspase/DIABLO release. Moreover, survivin-ΔEx3 is able to inhibit production of reactive oxygen species and can translocate from nucleus to cytosol to associate with apoptosis signal-regulating kinase 1 after activation of LTβR. Furthermore, survivin-ΔEx3 protects LTβR-mediated cell death in caspase-3-deficient MCF-7 cells. Thus, survivin-ΔEx3 is able to regulate both caspase-dependent and caspase-independent pathways, whereas inhibition of caspase-independent pathway is both sufficient and necessary for its protective effect on LTβR-mediated cell death.
| Original language | English |
|---|---|
| Pages (from-to) | 3051-3061 |
| Number of pages | 11 |
| Journal | Cancer Research |
| Volume | 66 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Mar 15 2006 |
Fingerprint
ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Inhibition of lymphotoxin-β receptor-mediated cell death by survivin-ΔEx3. / You, Ren In; Chen, Mei Chieh; Wang, Hsei Wei; Chou, Yang Chieh; Lin, Chi Hung; Hsieh, Shie Liang.
In: Cancer Research, Vol. 66, No. 6, 15.03.2006, p. 3051-3061.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Inhibition of lymphotoxin-β receptor-mediated cell death by survivin-ΔEx3
AU - You, Ren In
AU - Chen, Mei Chieh
AU - Wang, Hsei Wei
AU - Chou, Yang Chieh
AU - Lin, Chi Hung
AU - Hsieh, Shie Liang
PY - 2006/3/15
Y1 - 2006/3/15
N2 - TNFSF14/LIGHT is a member of the tumor necrosis factor superfamily that binds to lymphotoxin-β receptor (LTβR) to induce cell death via caspase-dependent and caspase-independent pathways. It has been shown that cellular inhibitor of apoptosis protein-1 inhibits cell death by binding to LTβR-TRAF2/TRAF3 complexes and caspases. In this study, we found that both Kaposi's sarcoma-associated herpesvirus K7 (KSHV-K7), a viral inhibitor of apoptosis protein, and the structurally related protein survivin-ΔEx3 could inhibit LTβR-mediated caspase-3 activation. However, only survivin-ΔEx3 could protect cells from LTβR-mediated cell death. The differential protective effects of survivin-ΔEx3 and KSHV-K7 can be attributed to the fact that survivin-ΔEx3, but not KSHV-K7, is able to maintain mitochondrial membrane potential and inhibit second mitochondria-derived activator of caspase/DIABLO release. Moreover, survivin-ΔEx3 is able to inhibit production of reactive oxygen species and can translocate from nucleus to cytosol to associate with apoptosis signal-regulating kinase 1 after activation of LTβR. Furthermore, survivin-ΔEx3 protects LTβR-mediated cell death in caspase-3-deficient MCF-7 cells. Thus, survivin-ΔEx3 is able to regulate both caspase-dependent and caspase-independent pathways, whereas inhibition of caspase-independent pathway is both sufficient and necessary for its protective effect on LTβR-mediated cell death.
AB - TNFSF14/LIGHT is a member of the tumor necrosis factor superfamily that binds to lymphotoxin-β receptor (LTβR) to induce cell death via caspase-dependent and caspase-independent pathways. It has been shown that cellular inhibitor of apoptosis protein-1 inhibits cell death by binding to LTβR-TRAF2/TRAF3 complexes and caspases. In this study, we found that both Kaposi's sarcoma-associated herpesvirus K7 (KSHV-K7), a viral inhibitor of apoptosis protein, and the structurally related protein survivin-ΔEx3 could inhibit LTβR-mediated caspase-3 activation. However, only survivin-ΔEx3 could protect cells from LTβR-mediated cell death. The differential protective effects of survivin-ΔEx3 and KSHV-K7 can be attributed to the fact that survivin-ΔEx3, but not KSHV-K7, is able to maintain mitochondrial membrane potential and inhibit second mitochondria-derived activator of caspase/DIABLO release. Moreover, survivin-ΔEx3 is able to inhibit production of reactive oxygen species and can translocate from nucleus to cytosol to associate with apoptosis signal-regulating kinase 1 after activation of LTβR. Furthermore, survivin-ΔEx3 protects LTβR-mediated cell death in caspase-3-deficient MCF-7 cells. Thus, survivin-ΔEx3 is able to regulate both caspase-dependent and caspase-independent pathways, whereas inhibition of caspase-independent pathway is both sufficient and necessary for its protective effect on LTβR-mediated cell death.
UR - http://www.scopus.com/inward/record.url?scp=33645531325&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33645531325&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-05-2479
DO - 10.1158/0008-5472.CAN-05-2479
M3 - Article
C2 - 16540654
AN - SCOPUS:33645531325
VL - 66
SP - 3051
EP - 3061
JO - Cancer Research
JF - Cancer Research
SN - 0008-5472
IS - 6
ER -