Ring of Change: CDC48/p97 Drives Protein Dynamics at Chromatin.
Ring of Change: CDC48/p97 Drives Protein Dynamics at Chromatin.
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DOI：
10.3389/fgene.2016.00073
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发表时间：
2016
影响因子：
3.7
通讯作者：
Hoppe T
中科院分区：
文献类型：
--
作者：
Franz A;Ackermann L;Hoppe T
与核 DNA 相关的蛋白质的动态组成是染色体生物学的基本特性。在染色质区室中，专用蛋白质复合物控制着基因组信息的准确合成和修复，并定义了染色体分离或转录等重要细胞过程中 DNA 压缩的状态。蛋白质复合物与 DNA 的意外或错误关联会对基因组完整性产生不利影响。因此，蛋白质复合物与 DNA 的结合是非常动态的，并且可以对细胞信号传导事件做出快速反应，这需要严格的时空控制。在这种情况下，环状 AAA+ ATP 酶 CDC48/p97 成为泛素或 SUMO 标记的蛋白质复合物的关键调节因子。从机制上讲，CDC48/p97 充当分离酶，促进从染色质中提取底物蛋白。因此，CDC48/p97 通过染色质结合蛋白复合物的定向分解或重排来驱动分子反应。与 p97 突变相关的人类病理反映了这种机制的重要性，包括神经退行性疾病、肿瘤发生和过早衰老。本综述重点关注对决定染色质环境中 CDC48/p97 功能的分子机制的最新见解，这与癌症和衰老研究尤其相关。
The dynamic composition of proteins associated with nuclear DNA is a fundamental property of chromosome biology. In the chromatin compartment dedicated protein complexes govern the accurate synthesis and repair of the genomic information and define the state of DNA compaction in vital cellular processes such as chromosome segregation or transcription. Unscheduled or faulty association of protein complexes with DNA has detrimental consequences on genome integrity. Consequently, the association of protein complexes with DNA is remarkably dynamic and can respond rapidly to cellular signaling events, which requires tight spatiotemporal control. In this context, the ring-like AAA+ ATPase CDC48/p97 emerges as a key regulator of protein complexes that are marked with ubiquitin or SUMO. Mechanistically, CDC48/p97 functions as a segregase facilitating the extraction of substrate proteins from the chromatin. As such, CDC48/p97 drives molecular reactions either by directed disassembly or rearrangement of chromatin-bound protein complexes. The importance of this mechanism is reflected by human pathologies linked to p97 mutations, including neurodegenerative disorders, oncogenesis, and premature aging. This review focuses on the recent insights into molecular mechanisms that determine CDC48/p97 function in the chromatin environment, which is particularly relevant for cancer and aging research.