Targeted delivery of a human Bcl-2-specific protein binder effectively induces apoptosis of cancer cells

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Bcl-2 family proteins are critical switches to control cell death and survival, and Bcl-2 is a key regulator in pro-survival signaling, causing various diseases including cancers. Bcl-2 has drawn a considerable attention as a potential target for developing a pro-apoptotic agent for cancers. We here present the development of a specific protein binder against human Bcl-2 and its cytosolic delivery to effectively induce apoptosis of cancer cells. The protein binder composed of leucine-rich repeat modules was selected for human Bcl-2, and its binding affinity was increased up to 60 nM through a modular evolution-based approach. The protein binder was efficiently delivered into cancer cells by an intracellular delivery system using a translocation domain from a bacterial exotoxin, resulting in a strong suppression of anti-apoptotic signaling in cancer cells. Our results demonstrate that the human Bcl-2-specific protein binder can act as a potent therapeutic agent for cancers.
Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
Issue Date
2020-05
Language
English
Article Type
Article
Citation

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v.526, no.2, pp.447 - 452

ISSN
0006-291X
DOI
10.1016/j.bbrc.2020.03.113
URI
http://hdl.handle.net/10203/274244
Appears in Collection
BS-Journal Papers(저널논문)
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