Oncogenic TPM3-ALK activation requires dimerization through the coiled-coil structure of TPM3
Copyright policy )Oncogenic TPM3-ALK activation requires dimerization through the coiled-coil structure of TPM3
Inflammatory myofibroblastic tumor (IMT) is a mesenchymal tumor that can arise from anywhere in the body. Anaplastic lymphoma kinase (ALK) gene rearrangements, most often resulting in the tropomyosin 3 (TPM3)-ALK fusion gene, are the main causes of IMT. However, the mechanism of malignant transformation in IMT has yet to be elucidated. The purpose of this study was to clarify the role of the TPM3 region in the transformation of IMT via TPM3-ALK. Lentivirus vectors containing a TPM3-ALK fusion gene lacking various lengths of TPM3 were constructed and expressed in HEK293T and NIH3T3 cell lines. Focus formation assay revealed loss of contact inhibition in NIH3T3 cells transfected with full-length TPM3-ALK, but not with ALK alone. Blue-native polyacrylamide gel electrophoresis (BN-PAGE) revealed that TPM3-ALK dimerization increased in proportion to the length of TPM3. Western blot showed phosphorylation of ALK, ERK1/2, and STAT3 in HEK293T cells transfected with TPM3-ALK. Thus, the coiled-coil structure of TPM3 contributes to the transforming ability of the TPM3-ALK fusion protein, and longer TPM3 region leads to higher dimer formation.
- University of Tokyo Hospital Japan
- University of Tokyo Japan
Oncogene Proteins, Fusion, Biophysics, Coiled-coil structure, Tropomyosin, Transfection, Biochemistry, Inflammatory myofibroblastic tumor, Mice, Neoplasms, Muscle Tissue, Animals, Humans, Anaplastic Lymphoma Kinase, Oncogene Fusion, Protein Interaction Domains and Motifs, Phosphorylation, Molecular Biology, Blue-native polyacrylamide gel electrophoresis, Receptor Protein-Tyrosine Kinases, Cell Biology, TPM3-ALK, Cell Transformation, Neoplastic, HEK293 Cells, NIH 3T3 Cells, Protein Multimerization, Signal Transduction
Oncogene Proteins, Fusion, Biophysics, Coiled-coil structure, Tropomyosin, Transfection, Biochemistry, Inflammatory myofibroblastic tumor, Mice, Neoplasms, Muscle Tissue, Animals, Humans, Anaplastic Lymphoma Kinase, Oncogene Fusion, Protein Interaction Domains and Motifs, Phosphorylation, Molecular Biology, Blue-native polyacrylamide gel electrophoresis, Receptor Protein-Tyrosine Kinases, Cell Biology, TPM3-ALK, Cell Transformation, Neoplastic, HEK293 Cells, NIH 3T3 Cells, Protein Multimerization, Signal Transduction
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