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Structure and function of MuvB complexes

Oncogene volume 41, pages 2909–2919 (2022)Cite this article

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Abstract

Proper progression through the cell-division cycle is critical to normal development and homeostasis and is necessarily misregulated in cancer. The key to cell-cycle regulation is the control of two waves of transcription that occur at the onset of DNA replication (S phase) and mitosis (M phase). MuvB complexes play a central role in the regulation of these genes. When cells are not actively dividing, the MuvB complex DREAM represses G1/S and G2/M genes. Remarkably, MuvB also forms activator complexes together with the oncogenic transcription factors B-MYB and FOXM1 that are required for the expression of the mitotic genes in G2/M. Despite this essential role in the control of cell division and the relationship to cancer, it has been unclear how MuvB complexes inhibit and stimulate gene expression. Here we review recent discoveries of MuvB structure and molecular interactions, including with nucleosomes and other chromatin-binding proteins, which have led to the first mechanistic models for the biochemical function of MuvB complexes.

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Fig. 1: Regulation of cell-cycle gene expression by MuvB and RB-E2F complexes.
Fig. 2: MuvB structure.
Fig. 3: Model for MuvB function in repression and activation of cell-cycle genes.

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Acknowledgements

Research in the authors’ laboratory is funded by grants from the National Institutes of Health (R01GM124148, R01GM127707, and R01CA228413 to S.M.R.). Figures 1 and 3 were created with BioRender.com.

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  1. Department of Chemistry and Biochemistry, University of California, Santa Cruz, CA, 95064, USA

    Gerd A. Müller, Anushweta Asthana & Seth M. Rubin

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GAM, AA and SMR wrote and edited the manuscript.

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Müller, G.A., Asthana, A. & Rubin, S.M. Structure and function of MuvB complexes. Oncogene 41, 2909–2919 (2022). https://doi.org/10.1038/s41388-022-02321-x

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