Inactivation of the p53 pathway in Retinoblastoma

This paper investigates the p53 status of Retinoblastoma tumors. They find that MDM4, the ubiquitin-ligase for p53, is amplified in Retinoblastoma tumors. Amplification of MDM4 allows the cells to maintain a wild-type p53 sequence but functionally inactivates p53. This method of inactivation of p53 function has been observed in other tumor types, but this paper proposes that the inactivation of Rb may select for inactivation of MDM4. This was presented at the UCSF BMS Journal Club on 1-18-07.