Differentiation specific functions of the Bin1 SH3 domain.
|Title:||Differentiation specific functions of the Bin1 SH3 domain.|
|Authors:||Sandoz, Jacqueline S.|
|Abstract:||A significant percentage of breast and prostate tumours have a missing or aberrantly expressed Bin1 protein. However, preliminary work in skeletal muscle has shown that Bin1 may also be involved in regulating differentiation. Based on the variable roles attributed to Bin1, we proposed a hypothesis in which distinct domains of Bin1 regulate different functions of the protein. This study examines one particular domain of Bin1, the SH3 domain, through a dominant negative approach in a mouse model. Overexpression of the SH3 domain using a broadly expressed promoter resulted in a skeletal muscle phenotype that included large myofibre diameter in vivo and an inability to complete the differentiation process in vitro. Importantly, these deficits were not accompanied by disruptions in apoptosis, increased cell proliferation or tumorigenesis. These results suggest that Bin1 has distinct functions that are mediated by the modular SH3 domain and separate from its role in cell cycle regulation.|
|Collection||Thèses, 1910 - 2010 // Theses, 1910 - 2010|