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Published on: July 30, 2014
Identification of a cofilin-like actin-binding site on translationally controlled tumor protein (TCTP)
Katsiaryna Tsarova1, Elena G Yarmola, Michael R Bubb
1North Florida/South Georgia Veterans Health System, Gainesville, FL, USA.
Abstract:
Translationally controlled tumor protein (TCTP) expression is suppressed during cancer cell reversion to a non-malignant phenotype. We identified a primary sequence of TCTP with homology to ADF/cofilin. We confirm that a synthetic peptide corresponding to this sequence binds specifically to actin and is displaced from actin by cofilin. TCTP peptide has higher affinity for G-actin than F-actin and does not block actin-filament depolymerization by cofilin. These results suggest that TCTP may channel active cofilin to F-actin, enhancing the cofilin-activity cycle in invasive tumor cells. Loss of TCTP may result in sequestration of active cofilin by a monomeric pool of actin.
Insights
Translationally controlled tumor protein (TCTP) suppresses cancer progression. TCTP peptides interact with actin and cofilin, potentially regulating actin dynamics in invasive tumor cells.
Area of Science:
- Molecular Biology
- Cell Biology
- Cancer Research
Background:
- Translationally controlled tumor protein (TCTP) expression is reduced in non-malignant cancer cells.
- TCTP shares sequence homology with actin-binding proteins like ADF/cofilin.
Purpose of the Study:
- To investigate the interaction between TCTP and actin.
- To elucidate the role of TCTP in regulating actin dynamics and cofilin activity in cancer cells.
Main Methods:
- Identification of a TCTP sequence homologous to ADF/cofilin.
- Synthesis of a TCTP peptide.
- In vitro actin-binding assays using purified actin, cofilin, and TCTP peptide.
- Assessment of TCTP peptide's affinity for G-actin versus F-actin.
- Evaluation of TCTP peptide's effect on cofilin-mediated actin depolymerization.
Main Results:
- A synthetic TCTP peptide specifically binds to actin.
- Actin-bound TCTP peptide is displaced by cofilin.
- TCTP peptide exhibits higher affinity for monomeric G-actin than filamentous F-actin.
- TCTP peptide does not inhibit cofilin-driven actin depolymerization.
Conclusions:
- TCTP may facilitate the interaction of cofilin with F-actin, thereby enhancing the cofilin-actin cycle in invasive tumor cells.
- Reduced TCTP levels in cancer cells could lead to the sequestration of active cofilin by monomeric actin, potentially impairing actin dynamics.
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