Caspase-dependent apoptosis of COS-7 cells induced by Bax overexpression: Differential effects of Bcl-2 and Bcl-x(L) on Bax-induced caspase activation and apoptosis

Chifumi Kitanaka, Takahiro Namiki, Kohji Noguchi, Toshihiro Mochizuki, Shigehide Kagaya, Shunji Chi, Akemi Hayashi, Akio Asai, Yoshihide Tsujimoto, Yoshiyuki Kuchino

研究成果: Article査読

56 被引用数 (Scopus)

抄録

Bcl-2 family proteins and ICE/CED-3 family proteases (caspases) are regarded as the basic regulators of apoptotic cell death. They are evolutionarily conserved and implicated in a variety of apoptosis. However, the precise mechanism by which these two families interact to regulate cell death is not yet known. In this study, we found that the overexpression of the Bcl-2 family member Bax induced apoptotic cell death in COS-7 cells through the activation of CPP32 (caspase-3)-like proteases that cleaved the DEVD tetrapeptide. This apoptotic cell death was suppressed by the viral proteins CrmA and p35, as well as by the chemically synthesized caspase inhibitors Z-Asp-CH2-DCB and zVAD-fmk. We also found that the Bax-induced apoptosis of COS-7 cells was suppressed by Bcl-x(L) and Ecl-2, though both Bcl-x(L) and Bcl-2 similarly prevented etoposide-induced apoptosis in COS-7 cells. In addition, Bcl-x(L) inhibited the activation of caspase-3-like proteases accompanying Bax-induced COS-7 cell death but Bcl-2 did not. These results indicate that the caspase activation is essential for Bax-induced apoptosis, and that the ability of Bcl-2 and Bcl-x(L) to prevent the Bax-induced caspase activation and apoptosis in COS-7 cells could be differentially regulated. Our results also suggest that Bcl-2 family proteins function upstream of caspase activation and control apoptosis through the regulation of caspase activity.

本文言語English
ページ(範囲)1763-1772
ページ数10
ジャーナルOncogene
15
15
DOI
出版ステータスPublished - 1997

ASJC Scopus subject areas

  • 分子生物学
  • 遺伝学
  • 癌研究

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