Abstract A17: Cell cycle control through DREAM and MMB complexes

The loss of cell cycle control is the most recognized trait of cancer cells. The ability of cells to exit the cell cycle has recently been shown to be dependent upon a large multi-protein repressor complex called DREAM. This complex represses the expression of all cell cycle genes during reversible cell cycle exit. In cycling cells, DREAM is disassembled and some of DREAM associated proteins form a new complex to promote cell cycle gene expression. These proteins that can act together both as repressors and activators of cell cycle gene expression are called the MuvB core. The MuvB core interacts with B-Myb during S phase to promote late cell cycle gene expression. This activator complex is called MMB and its integrity is required for proper cell division. The purpose of this project is to determine how the MuvB core interacts with B-Myb, and if MuvB can be targeted by therapeutics to restore proper cell cycle control in cancer. We have structurally and functionally characterized the mechanism of DREAM assembly and regulation, however MMB regulation remains poorly understood. DREAM has been suggested as a therapeutic target in cancer cells that arrest in response to drug treatment to evade apoptosis. Disruption of DREAM could force evasive cancer cells back into the cell cycle and elicit a response to chemotherapeutic treatment. Until recently, a DREAM interface to target was unavailable. I solved the x-ray crystal structure of MuvB core protein LIN52 complexed with RB tumor ...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Getting out of Cycle: G0 and Senescence: Poster Presentations - Proffered Abstracts Source Type: research