Rubin Lab

UCSC

Retinoblastoma Tumor Suppressor Pathway

Members of the E2F family of transcription factors activate genes required for DNA synthesis and cell cycle progression.  The retinoblastoma protein (Rb) binds and inhibits E2F until the cell is ready to begin S phase.  At this point, Rb is phosphorylated by cyclin-dependent kinases (Cdks) at multiple sites, E2F is released, and genes required for DNA synthesis and cell division are transcribed.  

 

The primary goal of our studies is to use atomic resolution structures and biophysical techniques to characterize the molecular interactions that stabilize the Rb-E2F complex and to understand how phosphorylation changes these interactions such that the complex dissociates.  We have found that phosphorylation of different Cdk sites induces diverse structural changes in Rb to modulate its different protein interactions.  We are also interested in developing small molecules that modulate Rb-E2F affinity.  This project is funded by the National Cancer Institute and Department of Defense Breast Cancer Research Program.