Current Understanding of the TCTP Interactome

Li, Siting; Ge, Feng

doi:10.1007/978-3-319-67591-6_5

Cited by 14 publications

(10 citation statements)

References 75 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The involvement of TCTP in a multitude of cell biological processes is reflected by the large number of interacting proteins. Compilations of the many interaction partners of TCTP have been published in the above-mentioned book [4][5][6]. A more recent study, using current proteomics approaches combined with in silico network and gene ontology enrichment analysis, identified 113 interacting proteins [7], which were allocated to the following gene network clusters: translation, stress response, cytoskeleton, signal transduction, proteasomes, nucleosomes and transcription, RNA binding and metabolic enzymes.…”

Section: Importance Of Tctp In Core Cell Biological and Stress Reactionsmentioning

confidence: 99%

Dysregulation of TCTP in Biological Processes and Diseases

Bommer

Telerman

2020

Cells

View full text Add to dashboard Cite

Translationally controlled tumor protein (TCTP), also called histamine releasing factor (HRF) or fortilin, is a multifunctional protein present in almost all eukaryotic organisms. TCTP is involved in a range of basic cell biological processes, such as promotion of growth and development, or cellular defense in response to biological stresses. Cellular TCTP levels are highly regulated in response to a variety of physiological signals, and regulatory mechanism at various levels have been elucidated. Given the importance of TCTP in maintaining cellular homeostasis, it is not surprising that dysregulation of this protein is associated with a range of disease processes. Here, we review recent progress that has been made in the characterisation of the basic biological functions of TCTP, in the description of mechanisms involved in regulating its cellular levels and in the understanding of dysregulation of TCTP, as it occurs in disease processes such as cancer.

show abstract

Section: Importance Of Tctp In Core Cell Biological and Stress Reactionsmentioning

confidence: 99%

Dysregulation of TCTP in Biological Processes and Diseases

Bommer

Telerman

2020

Cells

View full text Add to dashboard Cite

show abstract

“…TCTP is an evolutionary highly conserved protein with functions in cell growth, protein synthesis, cytoskeleton, immune response, development, malignant transformation, tumor reversion, induction of pluripotent stem cells and apoptosis. It interacts with a large number of proteins [ 3 ]. A direct interaction with the tumor suppressor p53, has been shown [ 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

A novel ligand of the translationally controlled tumor protein (TCTP) identified by virtual drug screening for cancer differentiation therapy

et al. 2021

View full text Add to dashboard Cite

SummaryIntroduction Differentiation therapy is a promising strategy for cancer treatment. The translationally controlled tumor protein (TCTP) is an encouraging target in this context. By now, this field of research is still at its infancy, which motivated us to perform a large-scale screening for the identification of novel ligands of TCTP. We studied the binding mode and the effect of TCTP blockade on the cell cycle in different cancer cell lines. Methods Based on the ZINC-database, we performed virtual screening of 2,556,750 compounds to analyze the binding of small molecules to TCTP. The in silico results were confirmed by microscale thermophoresis. The effect of the new ligand molecules was investigated on cancer cell survival, flow cytometric cell cycle analysis and protein expression by Western blotting and co-immunoprecipitation in MOLT-4, MDA-MB-231, SK-OV-3 and MCF-7 cells. Results Large-scale virtual screening by PyRx combined with molecular docking by AutoDock4 revealed five candidate compounds. By microscale thermophoresis, ZINC10157406 (6-(4-fluorophenyl)-2-[(8-methoxy-4-methyl-2-quinazolinyl)amino]-4(3H)-pyrimidinone) was identified as TCTP ligand with a KD of 0.87 ± 0.38. ZINC10157406 revealed growth inhibitory effects and caused G0/G1 cell cycle arrest in MOLT-4, SK-OV-3 and MCF-7 cells. ZINC10157406 (2 × IC50) downregulated TCTP expression by 86.70 ± 0.44% and upregulated p53 expression by 177.60 ± 12.46%. We validated ZINC10157406 binding to the p53 interaction site of TCTP and replacing p53 by co-immunoprecipitation. Discussion ZINC10157406 was identified as potent ligand of TCTP by in silico and in vitro methods. The compound bound to TCTP with a considerably higher affinity compared to artesunate as known TCTP inhibitor. We were able to demonstrate the effect of TCTP blockade at the p53 binding site, i.e. expression of TCTP decreased, whereas p53 expression increased. This effect was accompanied by a dose-dependent decrease of CDK2, CDK4, CDK, cyclin D1 and cyclin D3 causing a G0/G1 cell cycle arrest in MOLT-4, SK-OV-3 and MCF-7 cells. Our findings are supposed to stimulate further research on TCTP-specific small molecules for differentiation therapy in oncology.

show abstract

“…TCTP is a highly conserved protein that participates in various cellular processes, including cell growth, proliferation, and metabolism [6,7]. Emerging studies have found TCTP a key regulator in organ development, and its role in growth control is conserved in many eukaryotes [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

TCTP Promotes Hu Sheep Rumen Epithelial Development before Weaning

Zheng¹,

Wu²,

Guo³

et al. 2021

Preprint

View full text Add to dashboard Cite

BackgroundHu Sheep is a world precious breed of sheep. Rumen is the most important digestive organ for ruminant animals. A better understanding of the molecular mechanisms involved in rumen development help us design better strategies to improve the production of sheep. Translationally controlled tumor protein (TCTP) is a highly conserved protein that involves various cellular processes. However, its role in rumen epithelium development remains unknown.ResultsTCTP was expressed in stratum basale, stratum spinosum and stratum granulosum of rumen epithelium. TCTP mRNA expression was extremely high on the day of birth, it then significantly decreased on day 15 and gradually increased until day 45 of age. TCTP protein expression remained in a relative low level from day 0 to day 15 of age, it then significantly increased on day 30 and gradually decreased until day 60. The ratio of Ki67 positive cell in stratum basale cell followed the similar pattern as the expression of TCTP. The papillae length decreased at first 15 days of postnatal life. Thereafter, the papilla undergo a period of growth from 538.1±17.3μm to 2211.1±56.6μm until 60 days of age. The phosphorylation of AKT is the highest on day 15 of age, then decreased until day 45. The ratio of acetate:propionate in rumen fluid decreased from day 30 to day 60 of age. ConclusionsTCTP participates in rumen papillae growth by promoting rumen stratum basale cell proliferation. We suggest that the translation of TCTP mRNA is regulated by AKT phosphorylation and the development of rumen papillae is associated with acetate:propionate ratio.

show abstract

Current Understanding of the TCTP Interactome

Cited by 14 publications

References 75 publications

Dysregulation of TCTP in Biological Processes and Diseases

Dysregulation of TCTP in Biological Processes and Diseases

A novel ligand of the translationally controlled tumor protein (TCTP) identified by virtual drug screening for cancer differentiation therapy

TCTP Promotes Hu Sheep Rumen Epithelial Development before Weaning

Contact Info

Product

Resources

About