Details

Autor(en) / Beteiligte

• Degterev, A
• Lugovskoy, A
• Cardone, M
• Mulley, B
• Wagner, G
• Mitchison, T
• Yuan, J

Titel

Identification of small-molecule inhibitors of interaction between the BH3 domain and Bcl-xL

Ist Teil von

• Nature cell biology, 2001-02, Vol.3 (2), p.173-182

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2001

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• To study the role of the BH3 domain in mediating pro-apoptotic and anti-apoptotic activities of Bcl-2 family members, we identified a series of novel small molecules (BH3Is) that inhibit the binding of the Bak BH3 peptide to Bcl-xL. NMR analyses revealed that BH3Is target the BH3-binding pocket of Bcl-xL. Inhibitors specifically block the BH3-domain-mediated heterodimerization between Bcl-2 family members in vitro and in vivo and induce apoptosis. Our results indicate that BH3-dependent heterodimerization is the key function of anti-apoptotic Bcl-2 family members and is required for the maintenance of cellular homeostasis.