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.
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http://dx.doi.org/10.1080/10717544.2022.2122636 | DOI Listing |
IUBMB Life
January 2025
Department of General Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
Tamoxifen (TAM) is employed to treat premenopausal ER-positive breast cancer patients, but TAM resistance is the main reason affecting its efficacy. Thus, addressing TAM resistance is crucial for improving therapeutic outcomes. This study explored the potential role of Tinagl1, a secreted extracellular matrix protein, whose expression is compromised in TAM-resistant MCF-7 breast cancer cells (MCF-7R).
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January 2025
Department of Proteomics, Mass Spectrometry Laboratory, Center for Genetic Engineering and Biotechnology, 31 Avenue, Cubanacan, Playa, Havana, Cuba.
Keyhole limpet haemocyanins (KLH1 and KLH2) from , are multi-subunit oxygen-carrying metalloproteins of approximately 3900 amino acids, that are widely used as carrier proteins in conjugate vaccines and in immunotherapy. KLHs and their derived conjugate vaccines are poorly characterized by LC-MS/MS due to their very stable supramolecular structures with megadalton molecular mass, and their resistance to efficient digestion with standard protocols. KLH1 and KLH2 proteins were conjugated to the conserved P0 peptide (pP0), derived from the P0 acidic ribosomal protein of sp.
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January 2025
The First Affiliated Hospital of Zhengzhou University, Zhengzhou City, Henan Province, People's Republic of China.
NKTCL is a highly aggressive malignant tumor, especially prevalent in the southern regions of China. Although chemotherapy regimens based on ADM have achieved certain therapeutic effects in early treatment, the issue of ADM resistance severely limits the therapeutic efficacy and makes it difficult to improve patient survival rates. Our research results indicate that the expression level of APOC1 is closely related to the sensitivity of NKTCL cells to ADM.
View Article and Find Full Text PDFJ Clin Invest
January 2025
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University; State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China.
The pathogenesis of thoracic aortic aneurysm (TAA) in Marfan syndrome (MFS) is generally attributed to vascular smooth muscle cell (VSMC) pathologies. However, the role of immune cell-mediated inflammation remains elusive. Single-cell RNA sequencing identified a subset of CX3CR1+ macrophages mainly located in the intima in the aortic roots and ascending aortas of Fbn1C1041G/+ mice, further validated in MFS patients.
View Article and Find Full Text PDFJ Clin Invest
January 2025
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.
Stimulator of interferon genes (STING) agonists have been developed and tested in clinical trials for their antitumor activity. However, the specific cell population(s) responsible for such STING activation-induced antitumor immunity have not been completely understood. In this study, we demonstrated that endothelial STING expression was critical for STING agonist-induced antitumor activity.
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