RNA 聚合酶 II 转录延伸
中文名称
通路描述
真核生物 mRNA 合成延伸过程中的机制正被最新研究揭示。这些研究导致了预期地发现直接调节 RNA 聚合酶 II 活性的多种转录因子，以及许多延伸因子在其他基础过程（如 DNA 修复、重组等）中发挥作用的意外发现。转录机器和主要 RNA 聚合酶的结构特征在物种间是保守的。参与延伸的基因属于不同的类别，如管家基因、细胞周期调控基因、发育和分化特异性基因等。参与延伸的基因列表近年来不断增长，包括：TFIIS、DSIF、NELF、P-Tefb 等，它们参与药物诱导或序列依赖性阻滞；TFIIF、ELL、elongin、elongator 等，它们通过改变 Pol II 的 Km 和/或 Vmax 来增加延伸的催化速率；FACT、Paf1 和其他因子，它们参与染色质修饰；DNA 修复蛋白、RNA 加工和出口因子、19S 蛋白酶体以及众多其他因子（如 Spt5-Spt5、Paf1 和 NELF 复合物、FCP1P 等）（Arndt 和 Kane, 2003）。延伸还代表转录的持续阶段，在此过程中，多种 mRNA 加工因子的活性与转录通过结合 RNA 聚合酶（Pol II）而耦合。实现这种相互作用的关键事件之一是 Pol II CTD 的磷酸化差异。CTD 的磷酸化模式在转录过程中发生变化，特别是在延伸过程中最为显著。TFIIH 介导的 Ser5 磷酸化主要在启动子区域观察到，而 P-Tefb 介导的 Ser2 磷酸化主要在编码区、延伸过程中观察到。实验证据表明，RNA 加工因子与转录周期中不同修饰形式的聚合酶存在动态结合。 (Komarnitsky 等人，2000)。[Komarnitsky 等人 2000, Arndt & Kane 2003, Shilatifard 等人 2003]
英文描述
Trafficking of GluR2-containing AMPA receptors Trafficking of GluR2-containing receptors is governed by protein protein interactions that are regulated by phosphorylation events. GluR2 binds NSF and AP2 in the proximal C terminal region and binds PICK and GRIP1/2 in the extreme C terminal region. GluR2 interaction with NSF is necessary to maintain the synaptic levels of GluR2-containing AMPA receptors both at basal levels and under conditions of synaptic activity. GluR2 interaction with GRIP helps anchor AMPA receptors at the synapse. Phosphorylation of GluR2 at S880 disrupts GRIP interaction but allows binding of PICK. PICK is activated by Ca sensitive Protein kinase C (PKC). Under basal conditions, in hippocampal synapse, GluR2-containing AMPA receptors (GluR2/GluR3) constitutively recycle between the synapse and the endosome by endocytosis and exocytosis. GRIP anchors the receptors at the synapse while PICK interaction internalizes the receptors and NSF helps maintain the synaptic receptors. Cerebellar stellate cells mainly contain GluR3 homomers as Ca permeable receptors. The interaction of GluR3 and GRIP is disrupted by PICK interaction by phosphorylation of equivalent of S880 residue in GluR3. Under conditions of repetitive presynaptic activity, there is PICK dependent removal of GluR2-lacking AMPA receptors and selective incorporation of GluR2-containing AMPA receptors at the synapse. The GluR2-containing AMPA receptors are first delivered to the surface by PICK and mobilized to the synapse by NSF dependent mechanism (Liu SJ and Cull-Candy SG Nat Neurosci. 2005 Jun;8(6):768-75)
所含基因
13 个基因