Pore-Forming Structure and Bifunction of the Pro-Apoptotic Factor, Bax

概要

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Bax (Bcl-2 associated protein X) was purified as a partner of Bcl-2 that forms a heterodimer. Bax shares some conserved domains with Bcl-2 and is involved promoting or inducing apoptosis instead of inhibiting apoptosis. Since Bax forms heterodimers via BH3 domain with anti-apoptotic members of the Bcl-2 family, it is considered to induce apoptosis by antagonizing anti-apoptotic factors, such as Bcl-2 or Bcl-x_L. Homology modeling on the basis of the crystal structure of Bcl-x allowed us to construct the Bax structure, suggesting that Bax has greater potential to form channel pores than Bcl-x_L. A trace amount of Bax induces bacterial death. The lethal domain was identified and found to correspond to the pore-forming domain. In addition, the pore-forming domain has an ability to induce apoptosis as judged by the extent of DNA ladder formation and FITC-Annexin V binding. The apoptosis that induced the pore-forming domain of Bax was not inhibited by Bcl-2 or Bcl-x_L overexpression. Therefore, it is proposed that Bax has own activity to induce apoptosis without antagonizing the anti-apoptotic factors.
日本医科大学の論文
1999-03-25