Role of TCTP in Cell Biological and Disease Processes

Bommer, Ulrich‐Axel; Kawakami, Toshiaki

doi:10.3390/cells10092290

Cited by 11 publications

(7 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TCTP plays fundamental roles in the regulation of cell cycle progression, apoptosis, autophagy, survival, stress responses, growth and development, and cytokine-like activities, among others [ 30 ]. Given the multiplicity of roles it plays, dysregulation of TCTP can lead to cardiovascular and metabolic diseases including systemic and pulmonary arterial hypertension [ 31 ], atherosclerosis, diabetes, carcinogenesis, and allergic and inflammatory disorders [ 32 ].…”

Section: Tctp As An Intracellular Nak-atpase Suppressormentioning

confidence: 99%

Role of Translationally Controlled Tumor Protein (TCTP) in the Development of Hypertension and Related Diseases in Mouse Models

Maeng

Lee

2022

Biomedicines

View full text Add to dashboard Cite

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+ and K+ ion gradients across the plasma membrane, by binding to and inhibiting Na,K-ATPase. Studies with transgenic mice overexpressing TCTP (TCTP-TG) revealed the pathophysiological significance of TCTP in the development of systemic arterial hypertension. Overexpression of TCTP and inhibition of Na,K-ATPase result in the elevation of cytoplasmic Ca2+ levels, which increases the vascular contractility in the mice, leading to hypertension. Furthermore, studies using an animal model constructed by multiple mating of TCTP-TG with apolipoprotein E knockout mice (ApoE KO) indicated that TCTP-induced hypertension facilitates the severity of atherosclerotic lesions in vivo. This review attempts to discuss the mechanisms underlying TCTP-induced hypertension and related diseases gleaned from studies using genetically altered animal models and the potential of TCTP as a target in the therapy of hypertension-related pathological conditions.

show abstract

Section: Tctp As An Intracellular Nak-atpase Suppressormentioning

confidence: 99%

Role of Translationally Controlled Tumor Protein (TCTP) in the Development of Hypertension and Related Diseases in Mouse Models

Maeng

Lee

2022

Biomedicines

View full text Add to dashboard Cite

show abstract

“…Translationally Controlled Tumour Protein (TCTP) is a small (20 kDa) single-domain globular protein widely conserved across phyla. TCTP, also called fortilin or Histamine Release Factor (HRF), interacts with many partners [1] and is consistently involved in numerous biological processes including tumorigenesis and tumor reversion [2, 3, 4, 5, 6]. TCTP acts as an apoptosis inhibitor and promotes the proliferation of malignant cells.…”

Section: Introductionmentioning

confidence: 99%

“…Over the last twenty years, TCTP has become an attractive therapeutical target in cancers [2, 3, 4, 5, 6, 29, 30, 15]. The antidepressant sertraline drug went into phase I/II clinical studies against Acute Myeloid Leukemia (AML), alone or in combination with Ara-C [31].…”

Section: Introductionmentioning

confidence: 99%

Structural transitions in TCTP tumor protein upon Mcl-1 binding

Malard

Sizun

Thureau

et al. 2022

Preprint

View full text Add to dashboard Cite

Translationally Controlled Tumour Protein (TCTP) is a pro-survival factor in tumor cells. TCTP inhibits the mitochondrial apoptosis pathway by potentiating the anti-apoptotic Bcl-2 family members Mcl-1 and Bcl-xL. Specifically, TCTP binds Bcl-xL and inhibits the Bax-dependent Bcl-xL-induced cytochrome c release and TCTP reduces Mcl-1 turnover by inhibiting its ubiquitinylation, thus resulting in decreased Mcl-1 mediated apoptosis. TCTP owns a BH3-like motif forming a β-strand buried in the globular domain of the protein. The crystal structure of TCTP BH3-like peptide in complex with Bcl-xL highlighted the α-helical conformation of TCTP BH3-like motif, suggesting major changes in TCTP structure upon complex formation. However, the structural impact of the interaction on the full-length TCTP and the structural description of TCTP/Mcl-1 interaction are still lacking. Here using biophysical/biochemical methods (NMR, SAXS, circular dichroism, limited proteolysis), we provide an in-depth description of the TCTP/Mcl-1 complex. We demonstrate that full length TCTP binds to the BH3 binding groove of Mcl-1 via its BH3-like motif which interconverts between different binding modes at the micro- to milli-second timescale. As a consequence of the engagement of the BH3-like motif in the interface, the TCTP globular domain is destabilized into a molten-globule state. We also establish that the residue D16 in TCTP BH3-like motif is crucial for the stability and dynamics of the intermolecular interface. As a conclusion, we reveal here in details the structural plasticity of TCTP and discuss its implications for TCTP biology and for future anticancer drug design strategies aiming at targeting TCTP complexes.

show abstract

“…Translationally Controlled Tumor Protein (TCTP) is a small (20 kDa) single-domain globular protein widely conserved across phyla. TCTP, also called fortilin or Histamine Release Factor, interacts with many partners ( 1 ) and is consistently involved in numerous biological processes including tumorigenesis and tumor reversion ( 2 , 3 , 4 , 5 , 6 ). TCTP acts as an apoptosis inhibitor and promotes the proliferation of malignant cells.…”

mentioning

confidence: 99%

“…Over the last 20 years, TCTP has become an attractive therapeutical target in cancers ( 2 , 3 , 4 , 5 , 6 , 14 , 27 , 28 ). The antidepressant sertraline drug went into phase I/II clinical studies against Acute Myeloid Leukemia (AML), alone or in combination with Ara-C ( 29 ).…”

mentioning

confidence: 99%

Structural transitions in TCTP tumor protein upon binding to the anti-apoptotic protein family member Mcl-1

Malard

Sizun

Thureau

et al. 2023

Journal of Biological Chemistry

View full text Add to dashboard Cite

Role of TCTP in Cell Biological and Disease Processes

Abstract: Translationally controlled tumor protein (TCTP), also referred to as histamine-releasing factor (HRF) or fortilin, is a multifunctional protein, expressed in essentially all eukaryotic organisms [...]

Cited by 11 publications

References 27 publications

Role of Translationally Controlled Tumor Protein (TCTP) in the Development of Hypertension and Related Diseases in Mouse Models

Role of Translationally Controlled Tumor Protein (TCTP) in the Development of Hypertension and Related Diseases in Mouse Models

Structural transitions in TCTP tumor protein upon Mcl-1 binding

Structural transitions in TCTP tumor protein upon binding to the anti-apoptotic protein family member Mcl-1

Contact Info

Product

Resources

About