INT6 May Influence Breast Cancer Formation by Regulating the 26S Proteasome

摘要

Inactivation of int6 has been linked to breast cancer formation, but its molecular function and precise role in tumorigenesis are largely unknown. This project tests the hypothesis that into is a tumor suppressor gene, regulating the proteasome to mediate genetic stability and cell division. My data showed that Into formed a complex with the proteasome. If into expression is knocked down, proteasome becomes mis-assembled. These into- cells are hypersensitive to proteasome drug and show chromosome instability. To better understand the mechanism through which into regulates the proteasome, I have also completed a structure-function analysis to better understand the role of PCI domain in the Into protein and a manuscript describing this study has been submitted and under review. In addition to these progresses, I have just completed a photobleaching-based study analyzing proteasome mobility and movement in vivo, and how is this regulated by into. A manuscript describing this will be submitted in a month. In conclusion, this fellowship has allowed me to work very productively to decipher the function of into as a potential breast tumor suppressor.