Background on our resarch
Hamartin (TSC1) interacts with Polo-like kinase 1 (PLK1)
Previously we showed that during the G2/M transition of the cell cycle hamartin (TSC1) is phosphorylated by the CDK1/cyclin B1 complex. This phosphorylation event negatively regulates the activity of the hamartin/tuberin complex towards mTOR (Astrinidis et al. 2003 J. Biol. Chem.). Second, we found that the hamartin/tuberin complex interacts with the mitotic kinase Polo-like kinase 1 (PLK1). This interaction is mediated by hamartin residue T310 (Astrinidis et al. 2006 Hum. Mol. Genet.).
Cells without functional TSC1 or TSC2 are sensitive to PLK1 inhibitors
Recently we published that cells lacking TSC1 or TSC2 and LAM-derived tumor samples have increased PLK1 protein levels, and that PLK1 protein levels are regulated by mTOR activity. BI-2536 (a PLK1 inhibitor) caused a preferential decrease in the viability and survival, and an increase in cell death of TSC1 and TSC2 negative cells, compared to controls. Unexpectedly, BI-2536 stopped the pro-survival process of autophagy in TSC1 and TSC2 negative cells (Valianou et al. 2015 Cell Cycle). These studies we funded through grants from The LAM Foundation and the Department of Defense.
Previously we showed that during the G2/M transition of the cell cycle hamartin (TSC1) is phosphorylated by the CDK1/cyclin B1 complex. This phosphorylation event negatively regulates the activity of the hamartin/tuberin complex towards mTOR (Astrinidis et al. 2003 J. Biol. Chem.). Second, we found that the hamartin/tuberin complex interacts with the mitotic kinase Polo-like kinase 1 (PLK1). This interaction is mediated by hamartin residue T310 (Astrinidis et al. 2006 Hum. Mol. Genet.).
Cells without functional TSC1 or TSC2 are sensitive to PLK1 inhibitors
Recently we published that cells lacking TSC1 or TSC2 and LAM-derived tumor samples have increased PLK1 protein levels, and that PLK1 protein levels are regulated by mTOR activity. BI-2536 (a PLK1 inhibitor) caused a preferential decrease in the viability and survival, and an increase in cell death of TSC1 and TSC2 negative cells, compared to controls. Unexpectedly, BI-2536 stopped the pro-survival process of autophagy in TSC1 and TSC2 negative cells (Valianou et al. 2015 Cell Cycle). These studies we funded through grants from The LAM Foundation and the Department of Defense.