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A novel gene expression pathway regulated by nuclear phosphoinositides

机译:核磷酸肌醇调控的新型基因表达途径

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Phosphatidylinositol phosphate (PIP) kinases are responsible for the production of the lipid signaling molecule phosphatidylinositol 4,5-bisphosphate, PI4,5P_2. PI4,5P_2 can directly affect the function of an array of signal transduction pathways by interactions with PI4,5P2 effectors. PIP kinases modulate PI4,5P2 sensitive pathways by controlling the generation of P14,5P2 through interactions between PIP kinases and protein partners which target the PIP kinases to specific sub-cellular compartments. In addition, the protein partners are often themselves PI4,5P2 regulated proteins. PIP kinase targeting in this manner allows for the spatial and temporal generation of PI4,5P_2 to affect specific signaling pathways. Identification of these protein partners has allowed for the determination of many molecular mechanisms of PI4,5P2 signaling. Recently, a nuclear speckle targeted non-canonical poly(A) polymerase, Star-PAP, has been defined to have a functional interaction with the type Ialpha PIP kinase to process select mRNAs for their 3' end formation. Star-PAP contains a poly(A) polymerase catalytic and core domains (PAP) though it differs from the canonical PAP due to its unique domain arrangement and phosphoinositide regulation. Star-PAP is a duel specificity polymerase that harbors in vitro poly(A) polymerase activity that is stimulated by PI4.5P2, and also embodies features of Terminal Uridylyl Transferase (TUTase) in both of its domain arrangement and its in vitro ability to transfer UMP to cellular RNA including the small nuclear RNA U6. The Star-PAP complex of proteins contains a number of cleavage and polyadenylation components, an active PIPKIalpha capable of generating de novo PI4,5P_2, and the PI4,5P_2 sensitive protein kinase CKIalpha. CKIalpha can directly phosphorylate Star-PAP and, in conjunction with PIPKIa, is required for expression and maintenance of the Star-PAP target mRNA HO-1. HO-1 mRNA encodes the cytoprotective enzyme heme oxygenase-1, which ...
机译:磷脂酰肌醇磷酸酯(PIP)激酶负责脂质信号分子磷脂酰肌醇4,5-双磷酸酯PI4,5P_2的产生。 PI4,5P_2可通过与PI4,5P2效应子的相互作用直接影响一系列信号转导途径的功能。 PIP激酶通过控制P14激酶与蛋白伴侣之间的相互作用来控制P14,5P2的生成,从而调节PI4,5P2敏感途径,该伙伴将PIP激酶靶向特定的亚细胞区室。此外,蛋白质伴侣通常本身就是PI4,5P2调控的蛋白质。以这种方式靶向的PIP激酶允许在空间和时间上产生PI4,5P_2,以影响特定的信号传导途径。这些蛋白质伴侣的鉴定已允许确定PI4,5P2信号传导的许多分子机制。最近,核斑点靶向的非规范性聚(A)聚合酶Star-PAP已被定义为与Ialpha PIP激酶具有功能性相互作用,以处理为其3'端形成而选择的mRNA。尽管Star-PAP由于其独特的域排列和磷酸肌醇调节作用而不同于规范的PAP,但它包含一个poly(A)聚合酶催化域和核心域(PAP)。 Star-PAP是一种对决特异性聚合酶,具有PI4.5P2刺激的体外poly(A)聚合酶活性,并且在其域排列和体外转移能力方面都体现了末端Uridylyl Transferase(TUTase)的功能。 UMP到细胞RNA包括小核RNA U6。 Star-PAP蛋白质复合物包含许多切割和聚腺苷酸化成分,能够从头产生PI4,5P_2的活性PIPKIalpha和PI4,5P_2敏感的蛋白激酶CKIalpha。 CKIalpha可以直接磷酸化Star-PAP,并与PIPKIa一起表达和维持Star-PAP目标mRNA HO-1。 HO-1 mRNA编码细胞保护酶血红素加氧酶-1,该酶可...

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