Venue: Edificio Povo 2, via Sommarive nr. 9, Povo (Tn) - Room B102
At 2:00 p.m.
- Magdalena Karbowniczek - Department of Immunotherapeutics and Biotechnology, School of Pharmacy, Texas Tech University Health Sciences Center, Abilene, TX
Differentiation abnormalities are a hallmark of tuberous sclerosis complex (TSC) manifestations; however, the genesis of these abnormalities remains unclear. I will discuss the mechanisms controlling the unexpected multi-lineage, early neuronal progenitor and neural stem-like cell characteristics of lymphangioleiomyomatosis (LAM) and angiomyolipoma (AML) tumor cells. These mechanisms include the activation of a previously unreported Rheb-Notch-Rheb regulatory loop, in which the cyclic binding of Notch1 to the Notch-responsive elements (NREs) on the Rheb promoter is a key event. This binding induces the oscillatory transactivation of Rheb. The identified NRE2 on the Rheb promoter is essential to promoter activity. Notch cooperates with Rheb to restrict cell differentiation via similar mechanisms in mouse models of TSC. Cell specific loss of Tsc1 within nestin expressing cells in adult mice leads to the formation of kidney cysts, renal intraepithelial neoplasia and invasive papillary renal carcinoma.