Abstract
Diverse stimuli initiate the activation of apoptotic signaling pathways that often causes nuclear DNA fragmentation. Here, we report a new antiapoptotic protein, a caspase-activated DNase (CAD) inhibitor that interacts with ASK1 (CIIA). CIIA, by binding to apoptosis signal-regulating kinase 1 (ASK1), inhibits oligomerization-induced ASK1 activation. CIIA also associates with CAD and inhibits the nuclease activity of CAD without affecting caspase-3-mediated ICAD cleavage. Overexpressed CIIA reduces H2O 2- and tumor necrosis factor-α-induced apoptosis. CIIA antisense oligonucleotides, which abolish expression of endogenous CIIA in murine L929 cells, block the inhibitory effect of CIIA on ASK1 activation, deoxyribonucleic acid fragmentation, and apoptosis. These findings suggest that CIIA is an endogenous antagonist of both ASK1 - and CAD-mediated signaling.
| Original language | English |
|---|---|
| Pages (from-to) | 71-81 |
| Number of pages | 11 |
| Journal | Journal of Cell Biology |
| Volume | 163 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2003 Oct 13 |
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Keywords
- Apoptosis
- Apoptosis signal-regulating kinase 1
- C-Jun NH-terminal kinase
- Caspase-activated DNase
- Stress-activated protein kinase
ASJC Scopus subject areas
- Cell Biology
Cite this
Identification of a novel antiapoptotic protein that antagonizes ASK1 and CAD activities. / Cho, Ssang Goo; Kim, Jin Woo; Lee, Yong Hee; Hwang, Hyun Sub; Kim, Mi Sung; Ryoo, Kanghyun; Kim, Myung Jin; Noh, Kyung Tae; Kim, Eun Kyung; Cho, Jun Ho; Yoon, Kyoung Wan; Cho, Eun Gyung; Park, Hee Sae; Chi, Sung Wook; Lee, Min Jae; Kang, Sang Sun; Ichijo, Hidenori; Choi, Eui Ju.
In: Journal of Cell Biology, Vol. 163, No. 1, 13.10.2003, p. 71-81.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Identification of a novel antiapoptotic protein that antagonizes ASK1 and CAD activities
AU - Cho, Ssang Goo
AU - Kim, Jin Woo
AU - Lee, Yong Hee
AU - Hwang, Hyun Sub
AU - Kim, Mi Sung
AU - Ryoo, Kanghyun
AU - Kim, Myung Jin
AU - Noh, Kyung Tae
AU - Kim, Eun Kyung
AU - Cho, Jun Ho
AU - Yoon, Kyoung Wan
AU - Cho, Eun Gyung
AU - Park, Hee Sae
AU - Chi, Sung Wook
AU - Lee, Min Jae
AU - Kang, Sang Sun
AU - Ichijo, Hidenori
AU - Choi, Eui Ju
PY - 2003/10/13
Y1 - 2003/10/13
N2 - Diverse stimuli initiate the activation of apoptotic signaling pathways that often causes nuclear DNA fragmentation. Here, we report a new antiapoptotic protein, a caspase-activated DNase (CAD) inhibitor that interacts with ASK1 (CIIA). CIIA, by binding to apoptosis signal-regulating kinase 1 (ASK1), inhibits oligomerization-induced ASK1 activation. CIIA also associates with CAD and inhibits the nuclease activity of CAD without affecting caspase-3-mediated ICAD cleavage. Overexpressed CIIA reduces H2O 2- and tumor necrosis factor-α-induced apoptosis. CIIA antisense oligonucleotides, which abolish expression of endogenous CIIA in murine L929 cells, block the inhibitory effect of CIIA on ASK1 activation, deoxyribonucleic acid fragmentation, and apoptosis. These findings suggest that CIIA is an endogenous antagonist of both ASK1 - and CAD-mediated signaling.
AB - Diverse stimuli initiate the activation of apoptotic signaling pathways that often causes nuclear DNA fragmentation. Here, we report a new antiapoptotic protein, a caspase-activated DNase (CAD) inhibitor that interacts with ASK1 (CIIA). CIIA, by binding to apoptosis signal-regulating kinase 1 (ASK1), inhibits oligomerization-induced ASK1 activation. CIIA also associates with CAD and inhibits the nuclease activity of CAD without affecting caspase-3-mediated ICAD cleavage. Overexpressed CIIA reduces H2O 2- and tumor necrosis factor-α-induced apoptosis. CIIA antisense oligonucleotides, which abolish expression of endogenous CIIA in murine L929 cells, block the inhibitory effect of CIIA on ASK1 activation, deoxyribonucleic acid fragmentation, and apoptosis. These findings suggest that CIIA is an endogenous antagonist of both ASK1 - and CAD-mediated signaling.
KW - Apoptosis
KW - Apoptosis signal-regulating kinase 1
KW - C-Jun NH-terminal kinase
KW - Caspase-activated DNase
KW - Stress-activated protein kinase
UR - http://www.scopus.com/inward/record.url?scp=0142027916&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0142027916&partnerID=8YFLogxK
U2 - 10.1083/jcb.200303003
DO - 10.1083/jcb.200303003
M3 - Article
C2 - 14557248
AN - SCOPUS:0142027916
VL - 163
SP - 71
EP - 81
JO - Journal of Cell Biology
JF - Journal of Cell Biology
SN - 0021-9525
IS - 1
ER -