Tpr-met fusion protein
Tpr-Met fusion protein is an oncogene fusion protein consisting of TPR and MET.[1]
Contents
Structure
Tpr-Met was generated following a chromosomal rearrangement induced by the treatment of a human osteogenic sarcoma cell line with the carcinogen N-methyl-N'-nitronitrosoguanidine. The genomic rearrangement fuses two genetic loci,translocated promoter region, from chromosome 1q25 which encodes a dimerization leucine zipper motif, and MET, from chromosome 7q31 which contributes the kinase domain and carboxy-terminus of the Met RTK.[2][3] The resulting 65 kDa cytoplasmic Tpr-Met oncoprotein forms a dimer mediated through the Tpr leucine zipper.[4]
The Tpr-Met fusion protein lacks the extracellular, transmembrane and juxtamembrane domains of c-Met receptor, and has gained the Tpr dimerization motif, which allows constitutive and ligand-independent activation of the kinase. The loss of juxtamembrane sequences, necessary for the negative regulation of kinase activity and receptor degradation, prolongs duration of Met signalling.[5]
Experimental evidences
Effects in muscle
Skeletal muscle
Specific expression of Tpr-Met in terminally-differentiated skeletal muscle causes muscle wasting in vivo and exerts anti-differentiation effects in terminally differentiated myotubes.[6][7] Constitutive activation of MET signaling has been suggested to cause defects in myogenic differentiation, contributing to rhabdomyosarcoma development and progression.[8]
Cardiac muscle
In a transgenic model, cardiac-specific expression of Tpr-Met oncogene during postnatal life causes heart failure with early-onset.[9]
References
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External links
- Fusion Proteins, tpr-met at the US National Library of Medicine Medical Subject Headings (MeSH)
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