@article{3fc6c65321f6417c8c421565940cbf53,
title = "A Short Nur77-Derived Peptide Converts Bcl-2 from a Protector to a Killer",
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-XL.",
keywords = "CELLBIO, HUMDISEASE, PROTEINS",
author = "Kolluri, {Siva Kumar} and Xiuwen Zhu and Xin Zhou and Bingzhen Lin and Ya Chen and Kai Sun and Xuefei Tian and James Town and Xihua Cao and Feng Lin and Dayong Zhai and Shinichi Kitada and Frederick Luciano and Edmond O'Donnell and Yu Cao and Feng He and Jialing Lin and Reed, {John C.} and Satterthwait, {Arnold C.} and Zhang, {Xiao kun}",
note = "Funding Information: We thank S. Korsmeyer, S. Lowe, and S. Weintraub for knockout MEFs; K. Webster, D. Koch, J. Peng, D. King, R. Newlin, J. Meerloo, L. Wang, E. Monosov, N. Marshall, and Z. Zhang for technical assistance; D. Andrews for comments; and L. Frazer for preparation of the manuscript. This work was supported in part by grants to X-k.Z., J.C.R., A.C.S., and J.L. from the National Institutes of Health (CA109345, CA119785, GM060554, and GM062964), the US Army Medical Research and Material Command (W81XWH-08-1-0478 and DAMD17-03-1-0427), the California Tobacco-Related Diseases Research Program (CTRDRP) (11RT-0081), the California Breast Cancer Research Program (12IB-0168), the Susan G. Komen Breast Cancer Foundation (BCTR043351), and the 985 Project of Xiamen University. S.K.K. was supported by a new investigator award from CTRDRP and the Linus Pauling Institute at the Oregon State University. ",
year = "2008",
month = oct,
day = "7",
doi = "10.1016/j.ccr.2008.09.002",
language = "English (US)",
volume = "14",
pages = "285--298",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "4",
}