Protein transduction domain of translationally controlled tumor protein: characterization and application in drug delivery

Jeehye Maeng, Kyunglim Lee

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Our research group reported in 2011 the discovery of a novel cell-penetrating moiety in the N-terminus of the human translationally controlled tumor protein (TCTP). This moiety was responsible for the previously noted membrane translocating ability of purified full-length TCTP. The hydrophobic nature of TCTP-derived protein transduction domain (TCTP-PTD) endowed it with unique characteristics compared to other well-known cationic PTDs, such as TAT-PTD. TCTP-PTD internalizes partly through lipid-raft/caveolae-dependent endocytosis and partly by macropinocytosis. After cell entry, caveosome-laden TCTP-PTD appears to move to the cytoplasm and cytoskeleton except for the nucleus possibly through the movement to endoplasmic reticulum (ER). TCTP-PTD efficiently facilitates delivery of various types of cargos, such as peptides, proteins, and nucleic acids in vitro and in vivo. It is noteworthy that TCTP-PTD and its variants promote intranasal delivery of antidiabetics including, insulin and exendin-4 and of antigens for immunization in vivo, suggesting its potential for drug delivery. In this review, we attempted to describe recent advances in the understanding regarding the identification of TCTP-PTD, the characteristics of its cellular uptake, and the usefulness as a vehicle for delivery into cells of a variety of drugs and macromolecules. Our investigative efforts are continuing further to delineate the details of the functions and the regulatory mechanisms of TCTP-PTD-mediated cellular penetration and posttranslational modification of TCTP in physiologic and pathological processes. This is a review of what we currently know regarding TCTP-PTD and its use as a vehicle for the transduction of drugs and other molecules.

Original languageEnglish
Pages (from-to)3009-3021
Number of pages13
JournalDrug Delivery
Volume29
Issue number1
DOIs
StatePublished - 2022

Bibliographical note

Funding Information:
This research was supported by the Bio and Medical Technology Development Program (2020M3E5E2036808) and (2021R1A2C2003629) by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT).

Publisher Copyright:
© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

Keywords

  • Cell-penetrating peptide
  • drug delivery
  • protein transduction domain
  • translationally controlled tumor protein
  • translocation mechanism

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