Multifaceted behavior of PEST sequence enriched nuclear proteins in cancer biology and role in gene therapy.

Muhammad Sarfraz, Attia Afzal, Saadullah Khattak, Umair A K Saddozai, Hui-Min Li, Qian-Qian Zhang, Asadullah Madni, Kashif S Haleem, Shao-Feng Duan, Dong-Dong Wu, Shao-Ping Ji, Xin-Ying Ji

Journal of cellular physiology 2021 Mar

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The amino acid sequence enriched with proline (P), glutamic acid (E), serine (S), and threonine (T) (PEST) is a signal-transducing agent providing unique features to its substrate nuclear proteins (PEST-NPs). The PEST motif is responsible for particular posttranslational modifications (PTMs). These PTMs impart distinct properties to PEST-NPs that are responsible for their activation/inhibition, intracellular localization, and stability/degradation. PEST-NPs participate in cancer metabolism, immunity, and protein transcription as oncogenes or as tumor suppressors. Gene-based therapeutics are getting the attention of researchers because of their cell specificity. PEST-NPs are good targets to explore as cancer therapeutics. Insights into PTMs of PEST-NPs demonstrate that these proteins not only interact with each other but also recruit other proteins to/from their active site to promote/inhibit tumors. Thus, the role of PEST-NPs in cancer biology is multivariate. It is hard to obtain therapeutic objectives with single gene therapy. An especially designed combination gene therapy might be a promising strategy in cancer treatment. This review highlights the multifaceted behavior of PEST-NPs in cancer biology. We have summarized a number of studies to address the influence of structure and PEST-mediated PTMs on activation, localization, stability, and protein-protein interactions of PEST-NPs. We also recommend researchers to adopt a pragmatic approach in gene-based cancer therapy. © 2020 Wiley Periodicals LLC.

Citation

Muhammad Sarfraz, Attia Afzal, Saadullah Khattak, Umair A K Saddozai, Hui-Min Li, Qian-Qian Zhang, Asadullah Madni, Kashif S Haleem, Shao-Feng Duan, Dong-Dong Wu, Shao-Ping Ji, Xin-Ying Ji. Multifaceted behavior of PEST sequence enriched nuclear proteins in cancer biology and role in gene therapy. Journal of cellular physiology. 2021 Mar;236(3):1658-1676