Department of Chemistry and Biochemistry, University of California, Santa Cruz, CA, 95064, USA.
Oncogene. 2022 May;41(21):2909-2919. doi: 10.1038/s41388-022-02321-x. Epub 2022 Apr 26.
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.
细胞分裂周期的正常进程对于正常发育和内稳态至关重要，而在癌症中必然会失调。细胞周期调控的关键是控制在 DNA 复制（S 期）和有丝分裂（M 期）开始时发生的两波转录。MuvB 复合物在这些基因的调控中起着核心作用。当细胞不活跃分裂时，MuvB 复合物 DREAM 抑制 G1/S 和 G2/M 基因。值得注意的是，MuvB 还与致癌转录因子 B-MYB 和 FOXM1 形成激活复合物，这些复合物对于 G2/M 中有丝分裂基因的表达是必需的。尽管 MuvB 复合物在控制细胞分裂和与癌症的关系中具有重要作用，但尚不清楚 MuvB 复合物如何抑制和刺激基因表达。本文综述了 MuvB 结构和分子相互作用的最新发现，包括与核小体和其他染色质结合蛋白的相互作用，这些发现为 MuvB 复合物的生化功能提供了第一个机制模型。
