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首页> 外文期刊>Cell cycle >Raptor, a positive regulatory subunit of mTOR complex 1, is a novel phosphoprotein of the rDNA transcription machinery in nucleoli and chromosomal nucleolus organizer regions (NORs).
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Raptor, a positive regulatory subunit of mTOR complex 1, is a novel phosphoprotein of the rDNA transcription machinery in nucleoli and chromosomal nucleolus organizer regions (NORs).

机译：猛禽，mTOR复杂1的积极调节亚基，是核仁和染色体核仁组织者区域（NORs）中rDNA转录机制的新型磷蛋白。

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Raptor is the key scaffolding protein that recruits mTOR substrates to rapamycin-sensitive mTOR complex 1 (mTORC1), a molecular integrator of mitogenic and nutrient/energy environmental inputs into protein translation and cell growth. Although Raptor phosphorylation on various sites is pivotal in the regulation of mTORC1 activity, it remains to be elucidated whether site-specific phosphorylation differentially distributes Raptor to unique subcellular compartments. When exploring the spatiotemporal cell cycle dynamics of six different phospho (P)-Raptor isoforms (Thr ( 706) , Ser ( 722) , Ser ( 863) , Ser ( 792) and Ser ( 877) ), a number of remarkable events differentially defined a topological resetting of P-RaptorThr706 on interphasic and mitotic chromosomes. In interphase nuclei, P-Raptor (Thr706) co-localized with fibrillarin, a component of the nucleolar small nuclear ribonucleoprotein particle, as well as with RNA polymerase I, the enzyme that transcribes nucleolar rRNA. Upon Actinomycin D-induced nucleolar segregation and disaggregation, P-RaptorThr706 was excluded from the nucleolus to accumulate at discrete nucleoplasmic bodies. During mitosis, CDK1 inhibition-induced premature assembly of nucleoli relocated fibrillarin to the surrounding regions of chromosomal-associated P-Raptor (Thr706) , suggesting that a subpopulation of mitotic P-Raptor (Thr706) remained targeted at chromosomal loops of rDNA or nuclear organizer regions (NORs). At the end of mitosis and cytokinesis, when reassembly of incipient nucleoli begins upon NORs activation of rDNA transcription, fibrillarin spatially reorganized with P-Raptor (Thr706) to give rise to daughter nucleoli. Treatment with IGF1 exclusively hyperactivated nuclear P-Raptor (Ser706) and concomitantly promoted Ser ( 2481) autophosphorylation of mTOR, which monitors mTORC1-associated catalytic activity. Nucleolar- and NOR-associated P-Raptor (Ser706) may physically link mTORC1 signaling to ever-growing nucleolus plurifunctionality including ribosome biogenesis, cell stress sensor and cell cycle/aging control.
机译：猛禽是关键的支架蛋白，它将mTOR底物募集到雷帕霉素敏感的mTOR complex 1（mTORC1）中，该分子是有丝分裂和营养/能量环境输入到蛋白质翻译和细胞生长的分子整合剂。尽管猛禽在多个位点的磷酸化在调节mTORC1活性方面起着关键作用，但尚需阐明位点特异性磷酸化是否将猛禽区分到独特的亚细胞区室。当探索六种不同的磷酸（P）-Raptor同工型（Thr（706），Ser（722），Ser（863），Ser（792）和Ser（877））的时空细胞周期动态时，许多显着不同的事件在相间和有丝分裂染色体上定义了P-RaptorThr706的拓扑重置。在相间核中，P-Raptor（Thr706）与原纤维小核仁小核糖核蛋白颗粒的组成部分原纤维蛋白以及RNA聚合酶I（转录核仁rRNA的酶）共定位。在放线菌素D诱导的核仁分离和解离后，P-RaptorThr706从核仁中排除，以积累在离散的核质体上。在有丝分裂期间，CDK1抑制诱导的核仁过早组装将原纤维蛋白重新定位到染色体相关的P-Raptor（Thr706）的周围区域，这表明有丝分裂的P-Raptor（Thr706）的亚群仍然靶向rDNA或核组织者的染色体环。地区（NOR）。在有丝分裂和胞质分裂的末端，当最初核仁的重组在NORs激活rDNA转录后开始时，原纤维蛋白在空间上与P-Raptor（Thr706）重组，产生子核仁。用IGF1专门处理过活化的核P-Raptor（Ser706），并同时促进mTOR的Ser（2481）自磷酸化，从而监测mTORC1相关的催化活性。核仁和与NOR相关的P-Raptor（Ser706）可能将mTORC1信号传导与不断增长的核仁多能性联系起来，包括核糖体生物发生，细胞应激传感器和细胞周期/衰老控制。

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