Structural mechanism of Myb–MuvB assembly

Significance Myb family transcription factors are potent activators of cell proliferation and drivers of human cancer. B-Myb, the most ancient and conserved family member, induces transcription of mitotic genes. The MuvB complex, thought to be the master regulator of cell-cycle-dependent gene expression, is required for directing B-Myb to the proper promoters. We present a structural description of MuvB and how it recruits B-Myb. We identified a direct association between the B-Myb C-terminus and the MuvB components LIN9 and LIN52, and we determined the crystal structure of this subcomplex. Our data define LIN52 as a central transcription factor-binding hub in MuvB and reveal a Myb–MuvB interface that could be targeted with chemical inhibitors.