Structure and function of MuvB complexes.

Structure and function of MuvB complexes.
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MUVB复合物的结构和功能。

DOI:
10.1038/s41388-022-02321-x
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发表时间:
2022-05
期刊:
影响因子:
8
通讯作者:
Rubin, Seth M.
Rubin, Seth M.
中科院分区:
医学1区
文献类型:
--
作者:
Mueller, Gerd A.;Asthana, Anushweta;Rubin, Seth M.

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在细胞分裂周期中的适当进展对正常发育和动态平衡至关重要,在癌症中必然会受到错误的调控。细胞周期调控的关键是控制发生在DNA复制开始(S期)和有丝分裂(M期)的两个转录波。MuvB复合体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复合体DREAM抑制G1/S和G2/M基因。值得注意的是,MuvB还与G2/M中有丝分裂基因表达所需的致癌转录因子B-MYB和FOXM1形成激活复合体。尽管MuvB复合体在控制细胞分裂和与癌症的关系中发挥着重要作用,但MuvB复合体如何抑制和刺激基因表达尚不清楚。我们在这里回顾了MuvB结构和新的分子相互作用的发现,包括与核小体和其他染色质结合蛋白的相互作用,这导致了第一个关于该复合体生化功能的机制模型。
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 not been well understood how MuvB complexes inhibit and stimulate gene expression. We review here recent discoveries of MuvB structure and new molecular interactions, including with nucleosomes and other chromatin-binding proteins, which have led to the first mechanistic models for the biochemical function of the complex.
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