Ubiquitin proteasome system (UPS): what can chromatin do for you?
Ubiquitin proteasome system (UPS): what can chromatin do for you?
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DOI：
10.1016/j.ceb.2007.02.014
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发表时间：
2007-04-01
影响因子：
7.5
通讯作者：
Harper, J. Wade
中科院分区：
文献类型：
--
作者：
O'Connell, Brenda C.;Harper, J. Wade
Cul 4-Ddb 1是一种RING H2泛素连接酶，在DNA复制、DNA修复和转录等重要细胞过程中发挥重要作用。最近的研究揭示了Cul 4介导的信号通路和染色质生物学之间的密切联系。Cul 4-Ddb 1对底物的泛素化发生在染色质上，并由基于染色质的信号启动，该信号将Cul 4-Ddb 1募集到染色质或改变连接酶的活性。这包括Cul 4介导的复制许可因子Cdt 1的泛素化;这是一个需要染色质结合的PCNA和Cdt 2的过程，Cdt 2是最近确定的Cul 4候选底物受体家族的成员（称为Ddb 1和Cul 4相关因子：DCAFs）。另外两种基于Cul 4的泛素连接酶Cul 4-Ddb 1（Ddb 2）和Cul 4-Ddb 1（CSA）的活性受COP 9信号体的差异调节，以响应不同的基于染色质的信号。最后，Cul 4-Ddb 1直接修饰染色质的例子已经出现，包括历史的泛素化和参与染色质重塑或组蛋白甲基化的酶的招募。
Cul4-Ddb1, a RING H2 ubiquitin ligase, plays an important role in many vital cellular processes including DNA replication, DNA repair and transcription. Recent research reveals strong links between Cul4-mediated signaling pathways and chromatin biology. Ubiquitylation of substrates by Cul4-Ddb1 occurs on chromatin and is initiated by chromatin-based signals that either recruit Cul4-Ddb1 to chromatin or alter the activity of the ligase. This includes Cul4-mediated ubiquitylation of the replication licensing factor, Cdt1; a process that requires chromatin-bound PCNA and Cdt2, a member of the recently identified family of candidate substrate receptors for Cul4 (termed Ddb1- and Cul4-associated factors: DCAFs). The activity of two other Cul4-based ubiquitin ligases, Cul4-Ddb1(Ddb2) and Cul4-Ddb1(CSA), are differentially regulated by the COP9 signalosome in response to different chromatin-based signals. Finally, examples of direct modifications to chromatin by Cul4-Ddb1 have emerged, including ubiquitylation of histories and the recruitment of enzymes involved in chromatin remodeling or histone methylation.