Molecular mechanisms of the balance between function and inactivation of the Retinoblastoma Tumor Suppressor: effects of interactions with viral proteins

GONZALEZ FOUTEL N; DE PRAT-GAY G; CHEMES L.B.

Sierra de la Ventana

Conferencia; XLIII Reunión Annual de la Sociedad Argentina de Biofísica; 2014

Sociedad Argentina de BIofísica

The Retinoblastoma tumor suppressor (Rb) is a central regulator protein of the cell cycle, differentiation and chromatin structure in eukarytic cells. Rb participates in an extensive network of protein-protein interactions with more than 200 cellular targets, due the presence of two main binding sites: the E2F transcription factor binding site and the LxCxE linear motif. Rb is inactivated in many cancers both genetics and viral etiology. It has been found that pathogenic viruses such as HPV, SV40, and Adenovirus, mimic these cellular interaction motifs ?which are located in intrinsically disordered regions (IDR) -, enabling it to interact with Rb and take control of the cell. The hypotesis of this project is that viral proteins have distinct properties that establish interactions with pRb by promoting effective competition with cellular interactions. The main objective is to reveal the molecular basis of the loss of function of Rb by interactions with viral oncoproteins. We propose to characterize these interactions and study the molecular basis of the competition between viral and celullar targets for binding to Rb in in vitro and in vivo models. These studies will contribute by providing knowledge of the mechanisms and structure-function relationship of viral protein, linear motifs mediated interactions and also the development of future therapeutic strategies against cancer