Study on the novel S-phase specific proteolysis pathway

新型S期特异性蛋白水解途径的研究

• 批准号: 18570181
• 负责人: NISHITANI Hideo
• 金额: $ 2.63万
• 依托单位: University of Hyogo (2007)Kyushu University (2006)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18570181/
• 关键词: Cell Cycle; Aroteolvsis; replication; ubiauitin; PCNA; DNA複製

Cdt1, an essential factor for DNA replication licensing, is degraded soon after entry into S-phase. We discovered that two ubiquitin ligases, Skp2-Cul1 and DDB1-Cul4, independently recognize the N-terminus of Cdt1 for ubiquitination. The first 10 amino acid region of Cdt1 contains a conserved sequence, PCNA interacting motif (PIP-box). During S-phase, PCNA and DDB1-Cul4 co-operate to ubiquitinate Cdt1. This system also operates after DNA damage, such as UV irradiation. When PIP-box was mutated, Cdt1 became stable after UV irradiation, and during S-phase combined with silencing of Skp2. Many PCNA interacting proteins were isolated. Among them, we found that CDK inhibitor p21 is also degraded through PCNA and DDB1-Cul4 system. Though both Cdt1 and p21 play key roles during G1-phase, their presence after initiation of S-phase is not suitable for proper cell cycle progression., and thus should be degraded upon entry into S-phase. We propose that PCNA dependent DDB1-Cul4 ubiquitin system provides a feedback system that helps the coordination between end of G1-phase and initiation of S-phase.

CDT1是DNA复制许可的重要因素，在进入S期后不久就会退化。我们发现两个泛素连接酶SKP2-CUL1和DDB1-CUL4独立识别CDT1的N端用于泛素化。 CDT1的前10个氨基酸区域包含一个保守的序列PCNA相互作用基序（PIP-box）。在S期间，PCNA和DDB1-CUL4合作至泛素化CDT1。该系统还在DNA损伤（例如紫外线照射）后运行。当PIP盒被突变时，CDT1在紫外线照射后并在S期间与SKP2的沉默结合使用。分离了许多PCNA相互作用的蛋白。其中，我们发现CDK抑制剂P21也通过PCNA和DDB1-CUL4系统降解。尽管CDT1和P21在G1期间都起着关键作用，但它们在S期开始后的存在不适用于适当的细胞周期进程。我们建议PCNA依赖性DDB1-CUL4泛素系统提供了一个反馈系统，该系统有助于G1期和S期开始之间的配位。

项目成果

Two ubiquitin ligases, SCF-Skp2 and DDB1-Cul4, target human Cdtl for proteolysis

两种泛素连接酶 SCF-Skp2 和 DDB1-Cul4，靶向人 Cdtl 进行蛋白水解

• 发表时间: 2006
• 作者: 西谷 秀男;他
• 通讯作者: 他

染色体サイクル Cdt1タンパク質によるpre-RC形成と再複製の抑制制御

染色体周期 Cdt1 蛋白对前 RC 形成和再复制的抑制控制

• 发表时间: 2007
• 作者: Nishitani H;Sugimoto N;Roukos V;Nakanishi Y;Saijo M;Obuse C;Tsurimoto T;Fujit M;Lygerou Z;Nishimoto T;西谷 秀男
• 通讯作者: 西谷 秀男

Nuclear RanGAP is required for the heterochromatin assembly and is reciprocally regulated by histone H3 and Clr4 histone methyltransferase in Schizosaccharomyces pombe.

核 RanGAP 是异染色质组装所必需的，并且在粟酒裂殖酵母中受到组蛋白 H3 和 Clr4 组蛋白甲基转移酶的相互调节。

• 发表时间: 2006
• 期刊: Mol. Biol. Cell 17
• 作者: Nishijima;H.;Nakayama;JI.;Yoshioka;T.;Kusano;A.;Nishitani;H.;Shibahara;K-i.;Nishimoto;T.
• 通讯作者: T.

Licensing regulators Geminin and Cdt1 identify progenitor cells of the mouse CNS in a specific phase of the cell cycle

• DOI: 10.1016/j.neuroscience.2007.03.050
• 发表时间: 2007-06
• 期刊: Neuroscience
• 影响因子: 3.3
• 作者: M. Spella;O. Britz;Panorea Kotantaki;Z. Lygerou;H. Nishitani;R. Ramsay;C. Flordellis;F. Guillemot;T. Mantamadiotis;S. Taraviras

Cdtl associates dynamically with chromatin throughout G1 and recruits Geminin onto chromatin

Cdtl 在整个 G1 期间与染色质动态结合，并将 Geminin 募集到染色质上

• 发表时间: 2007
• 期刊: EMBO J. 26
• 作者: Xouri G;et. al.
• 通讯作者: et. al.