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The Role of the Pro-Survival Molecule Bfl-1 in Melanoma.
Abstract Bfl-1 is a pro-survival Bcl-2 family member overexpressed in a subset of chemoresistant tumours, including melanoma. Here, we characterised the expression and regulation of Bfl-1 in normal and malignant melanocytes and determined its role in protecting these cells from chemotherapy-induced apoptosis. Bfl-1 was mitochondrially resident in both resting and apoptotic cells and experienced regulation by the proteasome and NFκB pathways. siRNA-mediated knockdown enhanced sensitivity towards various relevant drug treatments, with forced overexpression of Bfl-1 protective. These findings identify Bfl-1 as a con...
Source: The International Journal of Biochemistry and Cell Biology - December 5, 2014 Category: Biochemistry Authors: Ck H, Mj C, Cl H, C C, S J, Ms C Tags: Int J Biochem Cell Biol Source Type: research

Tyro3-mediated phosphorylation of ACTN4 at tyrosines is FAK-dependent and decreases susceptibility to cleavage by m-Calpain.
In this study, we sought the molecular mechanism of Tyro3 effects avoiding endogenous background by overexpression of Tyro3 in fibroblasts that have negligible levels of Tyro3. This introduction triggers the tyrosyl-phosphorylation of ACTN4, a member of actin binding protein family involved in motility, a behavior critical for invasive progression, as shown by siRNA to Tyro3 limiting melanoma cell migration and invasion. Tyro3-mediated phosphorylation of ACTN4 required FAK activation at tyrosine 397 and the EGF receptor cascade, but not EGFR ligand binding. Using PCR-based mutagenesis, the sites of Tyro3-mediated ACTN4 pho...
Source: The International Journal of Biochemistry and Cell Biology - December 20, 2017 Category: Biochemistry Authors: Shao H, Wang A, Lauffenburger D, Wells A Tags: Int J Biochem Cell Biol Source Type: research