Dpt of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, 1 Rue Michel Servet, 1211 Genève 4, Switzerland.
Cell Signal. 2013 Apr;25(4):743-51. doi: 10.1016/j.cellsig.2012.12.018. Epub 2012 Dec 29.
The Ccr4-Not complex is a conserved multi-subunit complex in eukaryotes that carries 2 enzymatic activities: ubiquitination mediated by the Not4 RING E3 ligase and deadenylation mediated by the Ccr4 and Caf1 orthologs. This complex has been implicated in all aspects of the mRNA life cycle, from synthesis of mRNAs in the nucleus to their degradation in the cytoplasm. More recently the complex has also been implicated in many aspects of the life cycle of proteins, from quality control during synthesis of peptides, to assembly of protein complexes and protein degradation. Consistently, the Ccr4-Not complex is found both in the nucleus, where it is connected to transcribing ORFs, and in the cytoplasm, where it was revealed to be both associated with translating ribosomes and in RNA processing bodies. This functional and physical presence of the Ccr4-Not complex at all stages of gene expression raises the question of its fundamental role. This review will summarize recent evidence designing the Not3/5 module of the Ccr4-Not complex as a functional module involved in coordination of the regulation of gene expression between the nucleus and the cytoplasm.
Ccr4-Not 复合物是真核生物中保守的多亚基复合物，具有 2 种酶活性：由 Not4 RING E3 连接酶介导的泛素化和由 Ccr4 和 Caf1 同源物介导的脱腺苷酸化。该复合物参与 mRNA 生命周期的各个方面，从核内 mRNAs 的合成到细胞质中的降解。最近，该复合物还与蛋白质生命周期的许多方面有关，从肽合成过程中的质量控制，到蛋白质复合物的组装和蛋白质降解。一致地，Ccr4-Not 复合物既存在于细胞核中，与转录 ORF 相连，也存在于细胞质中，在细胞质中与翻译核糖体相关，并存在于 RNA 处理体中。Ccr4-Not 复合物在基因表达的所有阶段的这种功能和物理存在提出了其基本作用的问题。本综述将总结最近的证据，设计 Ccr4-Not 复合物的 Not3/5 模块作为参与协调核和细胞质中基因表达调控的功能模块。
