This research project aims to determine how the DREAM and Myb-MuvB (MMB) protein complexes regulate transcription to control cell proliferation. The conserved MuvB protein complex either represses or activates cell-cycle genes by timely association with specific DNA-binding transcription factors including E2F4-p130 (DREAM) and Myb (MMB). However, the biochemical function of the five protein MuvB complex is unknown. We propose and will test novel hypotheses for how MuvB associates with chromatin, how DREAM inhibits transcription by stabilizing chromatin structure, and how Myb activates gene expression through its association with MuvB. These studies will provide fundamental new insights regarding how the cell cycle is controlled and will uncover a novel mechanism for how transcription factors directly modulate gene expression through nucleosome positioning.
Project Health Relevance Tumor cells invariably have defects in the biochemical mechanisms that regulate cell growth and division, so understanding how these processes work is vital to understanding and inhibiting cancer. This project will determine a molecular picture of how protein complexes known as DREAM and Myb-MuvB control normal and cancer cell proliferation.
| Guiley, Keelan Z; Iness, Audra N; Saini, Siddharth et al. (2018) Structural mechanism of Myb-MuvB assembly. Proc Natl Acad Sci U S A 115:10016-10021 |
| Iness, Audra N; Felthousen, Jessica; Ananthapadmanabhan, Varsha et al. (2018) The cell cycle regulatory DREAM complex is disrupted by high expression of oncogenic B-Myb. Oncogene : |
