Development of a novel prostate apoptosis response-4 (Par-4) protein entity with an extended duration of action for therapeutic treatment of cancer.

Kyungbo Kim, Pereira Araujo, Nikhil Hebbar, Ziyuan Zhou, Xirong Zheng, Fang Zheng, Vivek M Rangnekar, Chang-Guo Zhan

Protein engineering, design & selection : PEDS 2019 Dec 13

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Prostate apoptosis response-4 (Par-4) is a tumor suppressor which protects against neoplastic transformation. Remarkably, Par-4 is capable of inducing apoptosis selectively in cancer cells without affecting the normal cells. In this study, we found that recombinant Par-4 protein had limited serum persistence in mice that may diminish its anti-tumor activity in vivo. To improve the in vivo performance of the short-lived Par-4 protein, we aimed to develop a novel, long-lasting form of Par-4 with extended sequence, denoted as Par-4Ex, without affecting the desirable molecular function of the natural Par-4. We demonstrate that the Par-4Ex protein entity, produced by using the Escherichia coli expression system suitable for large-scale production, fully retains the desirable pro-apoptotic activity of Par-4 protein, but with ~7-fold improved biological half-life. Further in vivo tests confirmed that, due to the prolonged biological half-life, the Par-4Ex protein is indeed more potent in suppressing metastatic tumor growth in mice. © The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Citation

Kyungbo Kim, Pereira Araujo, Nikhil Hebbar, Ziyuan Zhou, Xirong Zheng, Fang Zheng, Vivek M Rangnekar, Chang-Guo Zhan. Development of a novel prostate apoptosis response-4 (Par-4) protein entity with an extended duration of action for therapeutic treatment of cancer. Protein engineering, design & selection : PEDS. 2019 Dec 13;32(3):159-166