Identification of a novel antiapoptotic protein that antagonizes ASK1 and CAD activities

Ssang Goo Cho, Jin Woo Kim, Yong Hee Lee, Hyun Sub Hwang, Mi Sung Kim, Kanghyun Ryoo, Myung Jin Kim, Kyung Tae Noh, Eun Kyung Kim, Jun Ho Cho, Kyoung Wan Yoon, Eun Gyung Cho, Hee Sae Park, Sung Wook Chi, Min Jae Lee, Sang Sun Kang, Hidenori Ichijo, Eui Ju Choi

Research output: Contribution to journalArticle

38 Citations (Scopus)

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 languageEnglish
Pages (from-to)71-81
Number of pages11
JournalJournal of Cell Biology
Volume163
Issue number1
DOIs
Publication statusPublished - 2003 Oct 13

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

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  • Cite this

    Cho, S. G., Kim, J. W., Lee, Y. H., Hwang, H. S., Kim, M. S., Ryoo, K., Kim, M. J., Noh, K. T., Kim, E. K., Cho, J. H., Yoon, K. W., Cho, E. G., Park, H. S., Chi, S. W., Lee, M. J., Kang, S. S., Ichijo, H., & Choi, E. J. (2003). Identification of a novel antiapoptotic protein that antagonizes ASK1 and CAD activities. Journal of Cell Biology, 163(1), 71-81. https://doi.org/10.1083/jcb.200303003