Author/Authors :
Kolluri، نويسنده , , Siva Kumar and Zhu، نويسنده , , Xiuwen and Zhou، نويسنده , , Xin and Lin، نويسنده , , Bingzhen and Chen، نويسنده , , Ya and Sun، نويسنده , , Kai and Tian، نويسنده , , Xuefei and Town، نويسنده , , James and Cao، نويسنده , , Xihua and Lin، نويسنده , , Feng and Zhai، نويسنده , , Dayong and Kitada، نويسنده , , Shinichi and Luciano، نويسنده , , Frederick and OʹDonnell، نويسنده , , Edmond and Cao، نويسنده , , Yu and He، نويسنده , , Feng and Lin، نويسنده , , Jialing and Reed، نويسنده , , John C. and Satterthwait، نويسنده , , Arnold C. and Zhang، نويسنده , , Xiao-kun، نويسنده ,
Abstract :
Summary
can be converted into a proapoptotic molecule by nuclear receptor Nur77. However, the development of Bcl-2 converters as anticancer therapeutics has not been explored. Here we report the identification of a Nur77-derived Bcl-2-converting peptide with 9 amino acids (NuBCP-9) and its enantiomer, which induce apoptosis of cancer cells in vitro and in animals. The apoptotic effect of NuBCPs and their activation of Bax are not inhibited but rather potentiated by Bcl-2. NuBCP-9 and its enantiomer bind to the Bcl-2 loop, which shares the characteristics of structurally adaptable regions with many cancer-associated and signaling proteins. NuBCP-9s act as molecular switches to dislodge the Bcl-2 BH4 domain, exposing its BH3 domain, which in turn blocks the activity of antiapoptotic Bcl-XL.
