TP53 调控参与 G2 细胞周期停滞的基因转录
中文名称
通路描述
TP53 通过诱导 GADD45A 和 SFN 的转录以及抑制 CDC25C 的转录，建立 G2 停滞。TP53 与染色质修饰酶 EP300、PRMT1 和 CARM1 合作诱导 GADD45A 的转录。GADD45A 结合 Aurora 激酶 A（AURKA），抑制其催化活性，并阻止 AURKA 介导的 G2/M 转换。GADD45A 还与 PCNA 形成复合物。GADD45 与 PCNA 的相互作用对 S 期进展、G2 停滞和 DNA 修复的影响尚不清楚。SFN（14-3-3-σ）由 TP53 诱导（Hermeking 等人，1997），并通过结合 CDK1 和 CCNB1（ cyclin B1）的复合物，阻止其转位至细胞核，从而参与 G2 停滞。CDK1 和 CCNB1 复合物对核蛋白的磷酸化是 G2/M 转换所必需的（Chan 等人，1999）。虽然 SFN 促进 G2 停滞，但它也能同时抑制凋亡，通过结合 BAX 并阻止其转位至线粒体，这是细胞色素 C 释放步骤的一部分（Samuel 等人，2001）。TP53 与转录抑制因子 E2F4 合作结合 CDC25C 基因启动子，抑制 CDC25C 转录，从而维持 G2 停滞（St Clair 等人，2004；Benson 等人，2014）。锌指转录因子 ZNF385A（HZF）是 TP53 的直接转录靶点，可与 TP53 形成复合物，促进 TP53 介导的 SFN 转录（Das 等人，2007）。
英文描述
TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest TP53 contributes to the establishment of G2 arrest by inducing transcription of GADD45A and SFN, and by inhibiting transcription of CDC25C. TP53 induces GADD45A transcription in cooperation with chromatin modifying enzymes EP300, PRMT1 and CARM1 (An et al. 2004). GADD45A binds Aurora kinase A (AURKA), inhibiting its catalytic activity and preventing AURKA-mediated G2/M transition (Shao et al. 2006, Sanchez et al. 2010). GADD45A also forms a complex with PCNA. PCNA is involved in both normal and repair DNA synthesis. The effect of GADD45 interaction with PCNA, if any, on S phase progression, G2 arrest and DNA repair is not known (Smith et al. 1994, Hall et al. 1995, Sanchez et al. 2010, Kim et al. 2013). SFN (14-3-3-sigma) is induced by TP53 (Hermeking et al. 1997) and contributes to G2 arrest by binding to the complex of CDK1 and CCNB1 (cyclin B1) and preventing its translocation to the nucleus. Phosphorylation of a number of nuclear proteins by the complex of CDK1 and CCNB1 is needed for G2/M transition (Chan et al. 1999). While promoting G2 arrest, SFN can simultaneously inhibit apoptosis by binding to BAX and preventing its translocation to mitochondria, a step involved in cytochrome C release (Samuel et al. 2001). TP53 binds the promoter of the CDC25C gene in cooperation with the transcriptional repressor E2F4 and represses CDC25C transcription, thus maintaining G2 arrest (St Clair et al. 2004, Benson et al. 2014). The zinc finger transcription factor ZNF385A (HZF) is a direct transcriptional target of TP53 that can form a complex with TP53 and facilitate TP53-mediated induction of SFN transcription (Das et al. 2007).
所含基因
18 个基因