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Article ; Online: Inhibitors of dimerized translationally controlled tumor protein, a histamine releasing factor, may serve as anti-allergic drug candidates.

Maeng, Jeehye / Lee, Kyunglim

2023 Volume 211, Page(s) 141–152

Abstract: It has been established that translationally controlled tumor protein (TCTP), also called histamine releasing factor (HRF), exhibits cytokine-like activities associated with initiation of allergic responses only after forming dimers (dTCTP). Agents that ... ...

Abstract	It has been established that translationally controlled tumor protein (TCTP), also called histamine releasing factor (HRF), exhibits cytokine-like activities associated with initiation of allergic responses only after forming dimers (dTCTP). Agents that inhibit dTCTP by preventing its dimerization or otherwise block its function, also block development of allergic reactions, thereby serving as potential drugs to treat allergic diseases. Several lines of evidence have proven that peptides and antibodies that specifically inhibit the interactions between dTCTP and either its putative receptor or immunoglobulins exhibit significant in vivo efficacy as potential anti-inflammatory agents in murine models of allergic inflammatory diseases. This review highlights the development of several inhibitors targeting dTCTP and discusses how they affect the pathophysiological processes of allergic and inflammatory diseases in several animal models and offers new perspectives on anti-allergic drug discovery.
MeSH term(s)	Animals ; Mice ; Anti-Allergic Agents/pharmacology ; Anti-Allergic Agents/therapeutic use ; Dimerization ; Tumor Protein, Translationally-Controlled 1 ; Biomarkers, Tumor/metabolism ; Hypersensitivity/drug therapy ; Hypersensitivity/metabolism
Chemical Substances	Anti-Allergic Agents ; Tumor Protein, Translationally-Controlled 1 ; Biomarkers, Tumor
Language	English
Publishing date	2023-03-22
Publishing country	France
Document type	Journal Article ; Review
ZDB-ID	120345-9
ISSN	1638-6183 ; 0300-9084
ISSN (online)	1638-6183
ISSN	0300-9084
DOI	10.1016/j.biochi.2023.03.011
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Article: Role of Translationally Controlled Tumor Protein (TCTP) in the Development of Hypertension and Related Diseases in Mouse Models.

Maeng, Jeehye / Lee, Kyunglim

Biomedicines

2022 Volume 10, Issue 11

Abstract: Translationally controlled tumor protein (TCTP) is a multifunctional protein that plays a wide variety of physiological and pathological roles, including as a cytoplasmic repressor of Na,K-ATPase, an enzyme pivotal in maintaining ... ...

Abstract	Translationally controlled tumor protein (TCTP) is a multifunctional protein that plays a wide variety of physiological and pathological roles, including as a cytoplasmic repressor of Na,K-ATPase, an enzyme pivotal in maintaining Na
Language	English
Publishing date	2022-10-27
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines10112722
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Article: Systemic and brain delivery of antidiabetic peptides through nasal administration using cell-penetrating peptides.

Maeng, Jeehye / Lee, Kyunglim

Frontiers in pharmacology

2022 Volume 13, Page(s) 1068495

Abstract: The intranasal route has emerged as a promising strategy that can direct delivery of drugs into the systemic circulation because the high-vascularized nasal cavity, among other advantages, avoids the hepatic first-pass metabolism. The nose-to-brain ... ...

Abstract	The intranasal route has emerged as a promising strategy that can direct delivery of drugs into the systemic circulation because the high-vascularized nasal cavity, among other advantages, avoids the hepatic first-pass metabolism. The nose-to-brain pathway provides a non-invasive alternative to other routes for the delivery of macromolecular therapeutics. A great variety of methodologies has been developed to enhance the efficiency of transepithelial translocation of macromolecules. Among these, the use of cell-penetrating peptides (CPPs), short protein transduction domains (PTDs) that facilitate the intracellular transport of various bioactive molecules, has become an area of extensive research in the intranasal delivery of peptides and proteins either to systemic or to brain compartments. Some CPPs have been applied for the delivery of peptide antidiabetics, including insulin and exendin-4, for treating diabetes and Alzheimer's disease. This review highlights the current status of CPP-driven intranasal delivery of peptide drugs and its potential applicability as a universal vehicle in the nasal drug delivery.
Language	English
Publishing date	2022-11-14
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2022.1068495
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Article ; Online: Protein transduction domain of translationally controlled tumor protein: characterization and application in drug delivery.

Maeng, Jeehye / Lee, Kyunglim

Drug delivery

2022 Volume 29, Issue 1, Page(s) 3009–3021

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 ... ...

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.
MeSH term(s)	Administration, Intranasal ; Biomarkers, Tumor/metabolism ; Drug Delivery Systems ; Humans ; Insulin ; Tumor Protein, Translationally-Controlled 1
Chemical Substances	Biomarkers, Tumor ; Insulin ; Tumor Protein, Translationally-Controlled 1
Language	English
Publishing date	2022-07-29
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1213261-5
ISSN	1521-0464 ; 1071-7544
ISSN (online)	1521-0464
ISSN	1071-7544
DOI	10.1080/10717544.2022.2122636
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Article ; Online: A tryptophan-based assay method to search regulatory compounds for transcriptionally controlled tumor protein.

Jo, Seri / Jang, Eun-Hwa / Kim, Hwa Young / Lee, Kyunglim / Kim, Mi-Sun / Shin, Dong Hae

Biochemical and biophysical research communications

2023 Volume 692, Page(s) 149363

Abstract: Transcriptionally controlled tumor protein (TCTP) is a highly conserved protein performing a large number of cellular functions by binding with various partner proteins. The importance of its roles in many diseases requires an assay method to find ... ...

Abstract	Transcriptionally controlled tumor protein (TCTP) is a highly conserved protein performing a large number of cellular functions by binding with various partner proteins. The importance of its roles in many diseases requires an assay method to find regulatory compounds. However, the molecular characteristics of TCTP made it difficult to search for chemicals interacting with it. In this study, a tryptophan-based assay method was designed and Y151W mutant TCTP was constructed to search binding chemicals. Since there is no tryptophan in the native sequence of TCTP, the incorporation of tryptophan in the Y151W mutant was very effective to establish the method. A flavonoid library was employed to the assay with the method. With the native and Y151W mutant TCTPs, three flavonoids such as morin, myricetin and isobavachalcone have been found to interact with TCTP. Combined with native gel electrophoresis, the binding region of isobavachalcone was suggested to be the flexible loop of TCTP. This approach can be easily applicable to find binding compounds of proteins with similar molecular characteristics of TCTP.
MeSH term(s)	Humans ; Tryptophan ; Biomarkers, Tumor/metabolism ; Tumor Protein, Translationally-Controlled 1 ; Neoplasm Proteins/metabolism ; Neoplasms/metabolism
Chemical Substances	isobavachalcone (20784-50-3) ; Tryptophan (8DUH1N11BX) ; Biomarkers, Tumor ; Tumor Protein, Translationally-Controlled 1 ; Neoplasm Proteins
Language	English
Publishing date	2023-12-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	205723-2
ISSN	1090-2104 ; 0006-291X ; 0006-291X
ISSN (online)	1090-2104 ; 0006-291X
ISSN	0006-291X
DOI	10.1016/j.bbrc.2023.149363
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Article ; Online: Translationally controlled tumor protein restores impaired memory and altered synaptic protein expression in animal models of dementia.

Na, Eun Jung / Jeon, Yejin / Kim, Hyunju / Kim, Hye-Sun / Lee, Kyunglim / Kim, Hwa-Jung

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

2023 Volume 160, Page(s) 114357

Abstract: This study describes the effects of translationally controlled tumor protein (TCTP) on mice with memory impairment caused by scopolamine (SCO) administration. Specifically, memory functions and expression levels of hippocampal synaptic proteins in 7- to ... ...

Abstract	This study describes the effects of translationally controlled tumor protein (TCTP) on mice with memory impairment caused by scopolamine (SCO) administration. Specifically, memory functions and expression levels of hippocampal synaptic proteins in 7- to 12-month-old SCO-treated wild-type (WT-SCO) mice were compared to those of TCTP-overexpressing (TG) and TCTP knocked-down (KD) mice similarly treated with SCO. Passive-avoidance tasks were performed with WT, TG, and KD mice for four weeks after intraperitoneal injection of SCO or saline followed by an acquisition test. After completing behavioral studies, hippocampi of all mice groups were collected and their synaptic protein contents were subjected to Western blotting or immunohistochemical analyses, and compared with those of 5x familial Alzheimer's disease (5xFAD) mice and postmortem AD patients. Results of passive avoidance tests revealed that SCO-induced memory impairment was repaired in TCTP-TG mice, but not in TCTP-KD mice. Hippocampal expression levels of synaptophysin, synapsin-1, and PSD-95 were increased in TCTP-TG mice treated with SCO (TG-SCO) but decreased in TCTP-KD mice treated with SCO (KD-SCO). Decreased levels of TCTP, synaptophysin, and PSD-95 were also found in hippocampi of 5xFAD mice and AD patients. Expression levels of p-CREB/CREB and brain-derived neurotrophic factor (BDNF) in TCTP-TG and TG-SCO mice were similar to or increased compared to those in WT mice, but decreased in TCTP-KD and KD-SCO mice. BDNF immunoreactivity was restored in CA1 regions of hippocampi of TG-SCO mice, but not in KD-SCO mice. These results suggest that TCTP can restore damaged memory in mice possibly through restored synaptic protein expression.
MeSH term(s)	Mice ; Animals ; Brain-Derived Neurotrophic Factor/metabolism ; Synaptophysin/metabolism ; Tumor Protein, Translationally-Controlled 1 ; Memory Disorders/metabolism ; Scopolamine/pharmacology ; Hippocampus ; Alzheimer Disease/pathology ; Disease Models, Animal
Chemical Substances	Brain-Derived Neurotrophic Factor ; Synaptophysin ; Tumor Protein, Translationally-Controlled 1 ; Scopolamine (DL48G20X8X)
Language	English
Publishing date	2023-02-02
Publishing country	France
Document type	Journal Article
ZDB-ID	392415-4
ISSN	1950-6007 ; 0753-3322 ; 0300-0893
ISSN (online)	1950-6007
ISSN	0753-3322 ; 0300-0893
DOI	10.1016/j.biopha.2023.114357
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Article ; Online: Targeting the translationally controlled tumor protein by a monoclonal antibody improves allergic airway inflammation in mice.

Bae, Hae-Duck / Cho, Minyoung / Seo, Hyeran / Lyoo, In Kyoon / Lee, Kyunglim

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

2023 Volume 168, Page(s) 115655

Abstract: Secretion of translationally controlled tumor protein (TCTP) was found in body fluids during the late phase of allergic reactions, implicating TCTP in allergic diseases. Furthermore, blocking TCTP has been shown to be helpful in treating asthma and ... ...

Abstract	Secretion of translationally controlled tumor protein (TCTP) was found in body fluids during the late phase of allergic reactions, implicating TCTP in allergic diseases. Furthermore, blocking TCTP has been shown to be helpful in treating asthma and allergies in animal models. The objectives of this study were to produce anti-TCTP monoclonal antibodies (mAbs), test their ability to inhibit the cytokine-like function of dimeric TCTP (dTCTP) in vitro and to assess their therapeutic effects in a murine model of ovalbumin (OVA)-induced airway inflammation. We first verified the inhibitory effects of 4 anti-TCTP mAbs on dTCTP-induced secretion of IL-8 in BEAS-2B cells. To investigate the anti-inflammatory effect of anti-TCTP mAbs on allergic airway inflammation, we treated OVA-sensitized mice with anti-TCTP mAbs before OVA challenge. The changes in bronchoalveolar lavage fluid (BALF) cells, IL-4, IL-5, and IL-13 levels in both BALF and lung homogenates, plasma levels of OVA-specific IgE, and lung tissues were analyzed. We found that JEW-M449 anti-TCTP mAb bound to the flexible loop of TCTP and significantly inhibited dTCTP-induced IL-8 release, making it the most effective inhibitor in our study. We also found that treatment with JEW-M449 significantly reduced the infiltration of inflammatory cells and suppressed the OVA-induced upregulation of type 2 cytokines in both BALF and lung homogenates in a dose-dependent manner. In addition, JEW-M449 significantly attenuated the degree of goblet cell hyperplasia and mucus secretion. Our results demonstrate that specific targeting of the flexible loop of TCTP is a potent strategy for treating airway inflammatory diseases.
MeSH term(s)	Animals ; Mice ; Interleukin-8/pharmacology ; Tumor Protein, Translationally-Controlled 1 ; Asthma/metabolism ; Hypersensitivity/drug therapy ; Lung ; Inflammation/metabolism ; Cytokines/metabolism ; Bronchoalveolar Lavage Fluid ; Ovalbumin/pharmacology ; Mice, Inbred BALB C ; Disease Models, Animal
Chemical Substances	Interleukin-8 ; Tumor Protein, Translationally-Controlled 1 ; Cytokines ; Ovalbumin (9006-59-1)
Language	English
Publishing date	2023-10-06
Publishing country	France
Document type	Journal Article
ZDB-ID	392415-4
ISSN	1950-6007 ; 0753-3322 ; 0300-0893
ISSN (online)	1950-6007
ISSN	0753-3322 ; 0300-0893
DOI	10.1016/j.biopha.2023.115655
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Article: Dimerized translationally controlled tumor protein increases interleukin-8 expression through MAPK and NF-κB pathways in a human bronchial epithelial cell line.

Lee, Heewon / Lee, Kyunglim

Cell & bioscience

2018 Volume 8, Page(s) 13

Abstract: Background: Histamine releasing factor (HRF) is a unique cytokine known to regulate a variety of immune cells in late allergic reactions. In the previous study, we revealed that the biologically active form of HRF is the dimerized translationally ... ...

Abstract	Background: Histamine releasing factor (HRF) is a unique cytokine known to regulate a variety of immune cells in late allergic reactions. In the previous study, we revealed that the biologically active form of HRF is the dimerized translationally controlled tumor protein (dTCTP) for the first time, and confirmed the secretion of IL-8 cytokine by dTCTP in human bronchial epithelial cells. However, the signaling pathway by which dTCTP promotes the secretion of IL-8 is not known. Results: When the cells were stimulated with dTCTP, the canonical NF-κB pathway and ERK, JNK and p38 MAPK become activated. dTCTP promoted transcription of IL-8, which involved NF-κB and AP-1 transcription factors. NF-κB was found to be essential for the transcriptional activation of IL-8, while AP-1 was partially responsible for the transcriptional activation by dTCTP. p38 MAPK was found to be involved in post-transcriptional regulation of dTCTP by stabilizing IL-8 mRNA. Conclusions: This study demonstrated that dTCTP induces IL-8 secretion in BEAS-2B cells through transcriptional and post-transcriptional regulation of MAPK and NF-κB pathways. This study provides insight into the mechanism by which dTCTP induces inflammation.
Language	English
Publishing date	2018-02-20
Publishing country	England
Document type	Journal Article
ZDB-ID	2593367-X
ISSN	2045-3701
ISSN	2045-3701
DOI	10.1186/s13578-018-0214-6
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Article ; Online: Meclizine, a piperazine-derivative antihistamine, binds to dimerized translationally controlled tumor protein and attenuates allergic reactions in a mouse model.

Jang, Eun-Hwa / Bae, Hae-Duck / Jeon, Yejin / Shin, Dong Hae / Kang, Soosung / Lee, Kyunglim

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

2022 Volume 157, Page(s) 114072

Abstract: Translationally controlled tumor protein (TCTP), a highly conserved protein present in most eukaryotes, is involved in numerous biological processes. Only the dimeric form of TCTP (dTCTP) formed during inflammatory conditions exhibits cytokine-like ... ...

Abstract	Translationally controlled tumor protein (TCTP), a highly conserved protein present in most eukaryotes, is involved in numerous biological processes. Only the dimeric form of TCTP (dTCTP) formed during inflammatory conditions exhibits cytokine-like activity. Therefore, dTCTP is considered as a therapeutic target for allergic diseases. Because monomeric TCTP (mTCTP) and dTCTP share a high topological similarity, we hypothesized that small molecules interacting with mTCTP would also bind to dTCTP and interfere with dTCTP-based cellular processes. In this study, nine compounds listed in the literature as interacting with mTCTP were investigated for their ability to suppress the activity of extracellular dTCTP in bronchial epithelial cells. It was found that one of the nine, meclizine, a piperazine-derivative antihistamine, significantly reduced IL-8 release and suppressed the NF-κB pathway. The direct interaction of meclizine with dTCTP was confirmed by surface plasmon resonance (SPR). Also, we found that meclizine can attenuate ovalbumin (OVA)-induced airway inflammation in mice. Therefore, meclizine might be a potential anti-allergic drug as an inhibitor for dTCTP.
Language	English
Publishing date	2022-12-06
Publishing country	France
Document type	Journal Article
ZDB-ID	392415-4
ISSN	1950-6007 ; 0753-3322 ; 0300-0893
ISSN (online)	1950-6007
ISSN	0753-3322 ; 0300-0893
DOI	10.1016/j.biopha.2022.114072
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Article ; Online: Generation of Fel d 1 chain 2 genome-edited cats by CRISPR-Cas9 system.

Lee, Sang Ryeul / Lee, Kyung-Lim / Song, Seok-Hwan / Joo, Myeong-Don / Lee, Seo-Hyun / Kang, Ji-Su / Kang, Seon-Min / Idrees, Muhammad / Kim, Jae-Wook / Kong, Il-Keun

Scientific reports

2024 Volume 14, Issue 1, Page(s) 4987

Abstract: Allergens from domestic cats (Felis catus) cause allergy-related health problems worldwide. Fel d 1 is a major allergen that causes severe allergic reactions in humans, including rhinitis, conjunctivitis, and life-threatening asthma. Therefore, patients ... ...

Abstract	Allergens from domestic cats (Felis catus) cause allergy-related health problems worldwide. Fel d 1 is a major allergen that causes severe allergic reactions in humans, including rhinitis, conjunctivitis, and life-threatening asthma. Therefore, patients with cat allergies anticipate hypoallergenic cats. We successfully generated Fel d 1 chain 2 (CH2) genome-edited cats using the CRISPR-Cas9 system in this study. T7 endonuclease 1 assay and Sanger sequencing were used to confirm the mutation in CH2 genome-edited cats. Fel d 1 level in CH2 genome-edited cats were assessed by enzyme-linked immunosorbent assay (ELISA). Remarkably, ELISA showed that the level of Fel d 1 in the CH2 homozygous genome-edited cat (Name: Alsik) was extremely low compared with that in wild type domestic cats and could be hypoallergenic cats. Additionally, we successfully cloned the CH2 homozygous genome-edited cat using cytoplasm injection clone technology. The cloned CH2 homozygous genome-edited cat was verified using microsatellite analysis. Creating hypoallergenic cats using the CRISPR-Cas9 system is a significant step forward because these cats can safely approach allergic patients.
MeSH term(s)	Cats ; Animals ; Humans ; CRISPR-Cas Systems ; Hypersensitivity/complications ; Allergens/analysis ; Asthma/etiology ; Enzyme-Linked Immunosorbent Assay
Chemical Substances	Allergens
Language	English
Publishing date	2024-02-29
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-024-55464-0
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