Francesca Senic-Matuglia, Post-doc (»Add to Infobox)

Rubicon Fellow Pier Paolo Di Fiore's Group Academic: IFOM- FIRC Institute of Molecular Oncology, Milan Phone:  +39-02-574303301 Email:  francesca.senicifom-ieo-campus.it

General description: The Notch signalling cascade has been highly conserved throughout evolution, and plays a decisive role in the regulation of cell fate in both invertebrate and mammalian tissues. Aberrant Notch activation has been linked to human cancer. Since numerous genes participate in the modulation of the Notch pathway, a number of different mechanisms may be involved in the deregulation of Notch activity. One key regulator of the Notch pathway is the cell fate determinant Numb, a conserved protein which antagonizes Notch signaling during asymmetric cell division in embryogenesis. We found that, in breast cancers, there is frequent loss of Numb expression and that this causes increased activity of the Notch receptor. We are interested in understanding the role of the Numb/Notch pathway in human cancer. Role in RUBICON: We have uncovered a novel tumour suppressor circuitry involving a Numb/p53/Hdm2 ternary complex that affects ubiquitination and degradation of p53. We are now characterizing this complex in order to understand the mechanisms regulating the ubiquitination process within the complex.