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

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)159-166
Number of pages8
JournalProtein Engineering, Design and Selection
Volume32
Issue number3
DOIs
StatePublished - Dec 13 2019

Bibliographical note

Publisher Copyright:
© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Keywords

  • Par-4
  • biological half-life
  • metastatic cancer
  • protein engineering
  • therapeutic protein

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biochemistry
  • Molecular Biology

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