Prof. Zhang Xiaokun A short Nur77-derived peptide converts Bcl-2 from a protector to a killer

ProfessorZhang Xiaokun published a paper entitled: “A short Nur77-derived peptide converts Bcl-2 from a protector to a killer” onCancer Cell

Author： Zhang Xiaokun.etc

Abstract:

Bcl-2can be converted intoaproapoptotic molecule by nuclear receptorNur77. However, the development ofBcl-2converters as anticancer therapeutics has not been explored. Here we report the identification ofaNur77-derivedBcl-2-convertingpeptidewith 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 byBcl-2. NuBCP-9 and its enantiomer bindtotheBcl-2loop, Which shares the characteristics of structurally adaptable regions with many cancer-associated and signaling proteins. NuBCP-9s act as molecular switchestodislodge theBcl-2BH4 domain, exposing its BH3 domain, which in turn blocks the activity of antiapoptoticBcl-X-L.

DOI:10.1016/j.ccr.2008.09.002