| Literature DB >> 18835031 |
Siva Kumar Kolluri1, Xiuwen Zhu, Xin Zhou, Bingzhen Lin, Ya Chen, Kai Sun, Xuefei Tian, James Town, Xihua Cao, Feng Lin, Dayong Zhai, Shinichi Kitada, Frederick Luciano, Edmond O'Donnell, Yu Cao, Feng He, Jialing Lin, John C Reed, Arnold C Satterthwait, Xiao-kun Zhang.
Abstract
Bcl-2 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-X(L).Entities:
Mesh：
Substances：
Year: 2008 PMID： 18835031 PMCID： PMC2667967 DOI： 10.1016/j.ccr.2008.09.002
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743