GTSE1在G2/M进展中的作用
中文名称
通路描述
GTSE1（B99）是小鼠B99基因产生的微管相关蛋白，表现出细胞周期调控的表达，在G2期水平最高，并在TP53（p53）直接控制下表现出DNA损伤诱导的表达（Utrera et al. 1998, Collavin et al. 2000）。人类GTSE1与小鼠同源，结合微管，表现出细胞周期调控的表达，在G2期达到峰值，并在DNA损伤后参与G2检查点恢复，但不由TP53转录调控（Monte et al. 2003, Monte et al. 2004, Scolz et al. 2012）。在G1期，GTSE1位于微管晶格，可能直接结合微管蛋白。GTSE1与MAPRE1（EB1）之间的进化保守相互作用促进GTSE1定位至微管生长尖端，参与细胞迁移，可能与癌细胞侵袭性有关。高度侵袭性乳腺癌细胞系在G1期GTSE1水平高，而G1期GTSE1水平通常较低。在有丝分裂前期开始时，GTSE1可能由有丝分裂激酶（可能是CDK1）磷酸化，位于MAPRE1结合区域附近，导致GTSE1从微管正端解离（Scolz et al. 2012）。在G2检查点恢复（DNA损伤诱导G2阻滞后的细胞周期重入）期间，GTSE1重新定位至细胞核，结合TP53，并在MDM2依赖 manner下促进TP53细胞质转位和蛋白酶体介导的降解（Monte et al. 2003, Monte et al. 2004）。G2期GTSE1重新定位依赖于PLK1介导的GTSE1磷酸化（Liu et al. 2010）。GTSE1促进的TP53下调允许细胞在DNA损伤后避免TP53介导的凋亡并重新进入细胞周期（Monte et al. 2003）。虽然GTSE1在G2期介导的TP53下调与TP53靶基因（涉及凋亡和细胞周期阻滞）表达降低相关，但GTSE1也可增加TP53靶蛋白p21（CDKN1A）的半衰期。GTSE1介导的CDKN1A稳定涉及GTSE1与CDKN1A及其伴侣复合物（由HSP90和FKBPL组成，即WISp39）之间的相互作用，可能参与紫杉醇治疗的耐药性（Bublik et al. 2010）。
英文描述
Formation of the ureteric bud Visible kidney development initiates with the formation of the pronephros and then the mesonephros (reviewed in McMahon 2016). In amniotes these are transitory structures that are superseded by formation of the metanephros, the functional kidney that persists into adulthood. The nephric duct appears during development of the pronephros and then extends caudally in the mesonephros, inducing the formation of mesonephric tubules that drain into the nephric duct and provide blood filtration in the embryo. (The mesonephric duct is also called the Wolffian duct.)
Subsequently, the metanephros is initiated by formation of the ureteric bud in the nephric duct due to the interaction between the nephric duct and the adjacent metanephric mesenchyme. The ureteric bud will grow to become the ureter, branch further, and induce the formation of nephrons and collecting ducts at the termini of the branches (reviewed in Costantini 2012). Development of the ureteric bulge is regulated by reciprocal signals passed between the nephric duct and the metanephric mesenchyme (reviewed in Marcotte et al. 2014). Nephronectin (NPNT) secreted by the nephric duct interacts with Integrin alpha8/beta1 (ITGA8) on the metanephric mesenchyme to activate expression of GDNF in the metanephric mesenchyme (Brandenberger et al. 2001, Linton et al. 2007). GDNF secreted by the metanephric mesenchyme then binds and activates the RET tyrosine kinase located in the plasma membrane of nephric duct cells (Trupp et al. 1996, Majumdar et al. 2003). RET activates expression of WNT11 in the nephric duct to regulate differentiation (Majumdar et al. 2003). The extent of kidney development is circumscribed by inhibitory signals provided by ROBO2:SLIT at the duct-mesenchyme interface (Wainwright et al. 2015) and by FOXC1,2 from the paraxial mesoderm.
Subsequently, the metanephros is initiated by formation of the ureteric bud in the nephric duct due to the interaction between the nephric duct and the adjacent metanephric mesenchyme. The ureteric bud will grow to become the ureter, branch further, and induce the formation of nephrons and collecting ducts at the termini of the branches (reviewed in Costantini 2012). Development of the ureteric bulge is regulated by reciprocal signals passed between the nephric duct and the metanephric mesenchyme (reviewed in Marcotte et al. 2014). Nephronectin (NPNT) secreted by the nephric duct interacts with Integrin alpha8/beta1 (ITGA8) on the metanephric mesenchyme to activate expression of GDNF in the metanephric mesenchyme (Brandenberger et al. 2001, Linton et al. 2007). GDNF secreted by the metanephric mesenchyme then binds and activates the RET tyrosine kinase located in the plasma membrane of nephric duct cells (Trupp et al. 1996, Majumdar et al. 2003). RET activates expression of WNT11 in the nephric duct to regulate differentiation (Majumdar et al. 2003). The extent of kidney development is circumscribed by inhibitory signals provided by ROBO2:SLIT at the duct-mesenchyme interface (Wainwright et al. 2015) and by FOXC1,2 from the paraxial mesoderm.
所含基因
20 个基因