G1/S 特异性转录
中文名称
通路描述
E2F 转录因子家族调节细胞周期中从 G1 到 S 相位的转换。E2F 活性由视网膜母细胞瘤蛋白（pRb）家族成员调节，导致 E2F 响应基因的严格表达控制。pRb 由 Cyclin D:CDK 复合物磷酸化后从 E2F 释放，诱导 E2F 靶基因如 Cyclin E 的表达。E2F1 结合基因组上的 E2F 结合位点，激活目标蛋白的合成。为了注释目的，E2F1 调节的反应被归类在此通路中，并仅显示目标基因的注释信息。
E2F1 的细胞靶点包括胸苷酸合成酶（TYMS）（DeGregori 等 1995）、Rir2（RRM2）（DeGregori 等 1995, Giangrande 等 2004）、二氢叶酸还原酶（DHFR）（DeGregori 等 1995, Wells 等 1997, Darbinian 等 1999）、Cdc2（CDK1）（Furukawa 等 1994, DeGregori 等 1995, Zhu 等 2004）、Cyclin A1（CCNA1）（DeGregori 等 1995, Liu 等 1998）、CDC6（DeGregori 等 1995, Yan 等 1998; Ohtani 等 1998）、CDT1（Yoshida 和 Inoue 2004）、CDC45（Arata 等 2000）、Cyclin E（CCNE1）（Ohtani 等 1995）、Emi1（FBXO5）（Hsu 等 2002）以及 ORC1（Ohtani 等 1996, Ohtani 等 1998）。E2F1 激活 TK1（Dnk1）（Dou 等 1994, DeGregori 等 1995, Giangrande 等 2004）和 CDC25A（DeGregori 等 1995, Vigo 等 1999）在果蝇（Duronio 和 O'Farrell 1994, Reis 和 Edgar 2004）中是保守的。
RRM2 蛋白参与 dNTP 水平调节，该酶的激活导致 dNTP 水平升高，以预期 S 阶段。E2F1 对 RRM2 的激活已在果蝇中由 Duronio 和 O'Farrell（1994）证明。E2F1 对 CDC45 的激活在鼠细胞中使用人 E2F1 构建体（Arata 等 2000）已证明。Cyclin E 也受 E2F1 转录调节。Cyclin E 蛋白通过与 CDK2 结合在 G1 到 S 相位的转换中发挥重要作用（Ohtani 等 1996）。E2F1 介导的 PCNA 激活已在果蝇（Duronio 和 O'Farrell 1994）和某些人类细胞中使用重组腺病毒构建体（DeGregori 等 1995）证明。E2F1 介导的 DNA 聚合酶 alpha 亚基 p180（POLA1）激活已在某些人类细胞中证明。已在果蝇中由 Ohtani 和 Nevins（1994）证明。已在果蝇中发现 E2F1 诱导 Orc1 表达刺激 ORC1 6 复合物形成并结合到复制起点（Asano 和 Wharton 1999）。ORC1 6 招募 CDC6 和 CDT1，这些是招募 MCM2 7 复制解旋酶所必需的。E2F1 调节包含一个反馈机制，其中 Geminin（GMNN）可以通过与 CDC6/CDT1 相互作用抑制 ORC1 6 复合物对 MCM2 7 的招募。E2F1 激活 CDC25A 和 TK1（Dnk1）已在果蝇中推断出（Duronio RJ 和 O'Farrell 1994; Reis 和 Edgar 2004）。E2F1 激活 CDC25（String），后者激活 Cyclin B 和 CDK1 的复合物。这种现象已在鼠 NIH 3T3 细胞和 Rat1 细胞中观察到。
E2F1 的细胞靶点包括胸苷酸合成酶（TYMS）（DeGregori 等 1995）、Rir2（RRM2）（DeGregori 等 1995, Giangrande 等 2004）、二氢叶酸还原酶（DHFR）（DeGregori 等 1995, Wells 等 1997, Darbinian 等 1999）、Cdc2（CDK1）（Furukawa 等 1994, DeGregori 等 1995, Zhu 等 2004）、Cyclin A1（CCNA1）（DeGregori 等 1995, Liu 等 1998）、CDC6（DeGregori 等 1995, Yan 等 1998; Ohtani 等 1998）、CDT1（Yoshida 和 Inoue 2004）、CDC45（Arata 等 2000）、Cyclin E（CCNE1）（Ohtani 等 1995）、Emi1（FBXO5）（Hsu 等 2002）以及 ORC1（Ohtani 等 1996, Ohtani 等 1998）。E2F1 激活 TK1（Dnk1）（Dou 等 1994, DeGregori 等 1995, Giangrande 等 2004）和 CDC25A（DeGregori 等 1995, Vigo 等 1999）在果蝇（Duronio 和 O'Farrell 1994, Reis 和 Edgar 2004）中是保守的。
RRM2 蛋白参与 dNTP 水平调节，该酶的激活导致 dNTP 水平升高，以预期 S 阶段。E2F1 对 RRM2 的激活已在果蝇中由 Duronio 和 O'Farrell（1994）证明。E2F1 对 CDC45 的激活在鼠细胞中使用人 E2F1 构建体（Arata 等 2000）已证明。Cyclin E 也受 E2F1 转录调节。Cyclin E 蛋白通过与 CDK2 结合在 G1 到 S 相位的转换中发挥重要作用（Ohtani 等 1996）。E2F1 介导的 PCNA 激活已在果蝇（Duronio 和 O'Farrell 1994）和某些人类细胞中使用重组腺病毒构建体（DeGregori 等 1995）证明。E2F1 介导的 DNA 聚合酶 alpha 亚基 p180（POLA1）激活已在某些人类细胞中证明。已在果蝇中由 Ohtani 和 Nevins（1994）证明。已在果蝇中发现 E2F1 诱导 Orc1 表达刺激 ORC1 6 复合物形成并结合到复制起点（Asano 和 Wharton 1999）。ORC1 6 招募 CDC6 和 CDT1，这些是招募 MCM2 7 复制解旋酶所必需的。E2F1 调节包含一个反馈机制，其中 Geminin（GMNN）可以通过与 CDC6/CDT1 相互作用抑制 ORC1 6 复合物对 MCM2 7 的招募。E2F1 激活 CDC25A 和 TK1（Dnk1）已在果蝇中推断出（Duronio RJ 和 O'Farrell 1994; Reis 和 Edgar 2004）。E2F1 激活 CDC25（String），后者激活 Cyclin B 和 CDK1 的复合物。这种现象已在鼠 NIH 3T3 细胞和 Rat1 细胞中观察到。
英文描述
G1/S-Specific Transcription The E2F family of transcription factors regulate the transition from the G1 to the S phase in the cell cycle. E2F activity is regulated by members of the retinoblastoma protein (pRb) family, resulting in the tight control of the expression of E2F-responsive genes. Phosphorylation of pRb by cyclin D:CDK complexes releases pRb from E2F, inducing E2F-targeted genes such as cyclin E.E2F1 binds to E2F binding sites on the genome activating the synthesis of the target proteins. For annotation purposes, the reactions regulated by E2F1 are grouped under this pathway and information about the target genes alone are displayed for annotation purposes.
Cellular targets for activation by E2F1 include thymidylate synthase (TYMS) (DeGregori et al. 1995), Rir2 (RRM2) (DeGregori et al. 1995, Giangrande et al. 2004), Dihydrofolate reductase (DHFR) (DeGregori et al. 1995, Wells et al. 1997, Darbinian et al. 1999), Cdc2 (CDK1) (Furukawa et al. 1994, DeGregori et al. 1995, Zhu et al. 2004), Cyclin A1 (CCNA1) (DeGregori et al. 1995, Liu et al. 1998), CDC6 (DeGregori et al. 1995, Yan et al. 1998; Ohtani et al. 1998), CDT1 (Yoshida and Inoue 2004), CDC45 (Arata et al. 2000), Cyclin E (CCNE1) (Ohtani et al. 1995), Emi1 (FBXO5) (Hsu et al. 2002), and ORC1 (Ohtani et al. 1996, Ohtani et al. 1998). The activation of TK1 (Dnk1) (Dou et al. 1994, DeGregori et al. 1995, Giangrande et al. 2004) and CDC25A (DeGregori et al. 1995, Vigo et al. 1999) by E2F1 is conserved in Drosophila (Duronio and O'Farrell 1994, Reis and Edgar 2004).
RRM2 protein is involved in dNTP level regulation and activation of this enzyme results in higher levels of dNTPs in anticipation of S phase. E2F activation of RRM2 has been shown also in Drosophila by Duronio and O'Farrell (1994). E2F1 activation of CDC45 is shown in mouse cells by using human E2F1 construct (Arata et al. 2000). Cyclin E is also transcriptionally regulated by E2F1. Cyclin E protein plays important role in the transition of G1 in S phase by associating with CDK2 (Ohtani et al. 1996). E2F1-mediated activation of PCNA has been demonstrated in Drosophila (Duronio and O'Farrell 1994) and in some human cells by using recombinant adenovirus constructs (DeGregori et al. 1995). E2F1-mediated activation of the DNA polymerase alpha subunit p180 (POLA1) has been demonstrated in some human cells. It has also been demonstrated in Drosophila by Ohtani and Nevins (1994). It has been observed in Drosophila that E2F1 induced expression of Orc1 stimulates ORC1 6 complex formation and binding to the origin of replication (Asano and Wharton 1999). ORC1 6 recruit CDC6 and CDT1 that are required to recruit the MCM2 7 replication helicases. E2F1 regulation incorporates a feedback mechanism wherein Geminin (GMNN) can inhibit MCM2 7 recruitment of ORC1 6 complex by interacting with CDC6/CDT1. The activation of CDC25A and TK1 (Dnk1) by E2F1 has been inferred from similar events in Drosophila (Duronio RJ and O'Farrell 1994; Reis and Edgar 2004). E2F1 activates string (CDC25) that in turn activates the complex of Cyclin B and CDK1. A similar phenomenon has been observed in mouse NIH 3T3 cells and in Rat1 cells.
Cellular targets for activation by E2F1 include thymidylate synthase (TYMS) (DeGregori et al. 1995), Rir2 (RRM2) (DeGregori et al. 1995, Giangrande et al. 2004), Dihydrofolate reductase (DHFR) (DeGregori et al. 1995, Wells et al. 1997, Darbinian et al. 1999), Cdc2 (CDK1) (Furukawa et al. 1994, DeGregori et al. 1995, Zhu et al. 2004), Cyclin A1 (CCNA1) (DeGregori et al. 1995, Liu et al. 1998), CDC6 (DeGregori et al. 1995, Yan et al. 1998; Ohtani et al. 1998), CDT1 (Yoshida and Inoue 2004), CDC45 (Arata et al. 2000), Cyclin E (CCNE1) (Ohtani et al. 1995), Emi1 (FBXO5) (Hsu et al. 2002), and ORC1 (Ohtani et al. 1996, Ohtani et al. 1998). The activation of TK1 (Dnk1) (Dou et al. 1994, DeGregori et al. 1995, Giangrande et al. 2004) and CDC25A (DeGregori et al. 1995, Vigo et al. 1999) by E2F1 is conserved in Drosophila (Duronio and O'Farrell 1994, Reis and Edgar 2004).
RRM2 protein is involved in dNTP level regulation and activation of this enzyme results in higher levels of dNTPs in anticipation of S phase. E2F activation of RRM2 has been shown also in Drosophila by Duronio and O'Farrell (1994). E2F1 activation of CDC45 is shown in mouse cells by using human E2F1 construct (Arata et al. 2000). Cyclin E is also transcriptionally regulated by E2F1. Cyclin E protein plays important role in the transition of G1 in S phase by associating with CDK2 (Ohtani et al. 1996). E2F1-mediated activation of PCNA has been demonstrated in Drosophila (Duronio and O'Farrell 1994) and in some human cells by using recombinant adenovirus constructs (DeGregori et al. 1995). E2F1-mediated activation of the DNA polymerase alpha subunit p180 (POLA1) has been demonstrated in some human cells. It has also been demonstrated in Drosophila by Ohtani and Nevins (1994). It has been observed in Drosophila that E2F1 induced expression of Orc1 stimulates ORC1 6 complex formation and binding to the origin of replication (Asano and Wharton 1999). ORC1 6 recruit CDC6 and CDT1 that are required to recruit the MCM2 7 replication helicases. E2F1 regulation incorporates a feedback mechanism wherein Geminin (GMNN) can inhibit MCM2 7 recruitment of ORC1 6 complex by interacting with CDC6/CDT1. The activation of CDC25A and TK1 (Dnk1) by E2F1 has been inferred from similar events in Drosophila (Duronio RJ and O'Farrell 1994; Reis and Edgar 2004). E2F1 activates string (CDC25) that in turn activates the complex of Cyclin B and CDK1. A similar phenomenon has been observed in mouse NIH 3T3 cells and in Rat1 cells.
所含基因
28 个基因