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Targeted delivery of a human Bcl-2-specific protein binder effectively induces apoptosis of cancer cells.
- Source :
-
Biochemical & Biophysical Research Communications . May2020, Vol. 526 Issue 2, p447-452. 6p. - Publication Year :
- 2020
-
Abstract
- 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. • We developed a protein binder which specifically binds to human Bcl-2. • The protein binder was selected against human Bcl-2 through phage display, and its binding affinity was matured by a modular approach. • Efficient intracellular delivery of the protein binder led to a significant suppression of anti-apoptotic signaling in cancer cells. • The protein binder showed a strong cytotoxicity against cancer cells in EGFR-specific manner, implying its great therapeutic potential. [ABSTRACT FROM AUTHOR]
- Subjects :
- *CANCER cells
*BCL-2 proteins
*PROTEINS
*CELL death
*EXOTOXIN
*APOPTOSIS
Subjects
Details
- Language :
- English
- ISSN :
- 0006291X
- Volume :
- 526
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Biochemical & Biophysical Research Communications
- Publication Type :
- Academic Journal
- Accession number :
- 142929828
- Full Text :
- https://doi.org/10.1016/j.bbrc.2020.03.113