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首页> 外文期刊>Molecular and Cellular Biology >PTEN Represses RNA Polymerase III-Dependent Transcription by Targeting the TFIIIB Complex
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PTEN Represses RNA Polymerase III-Dependent Transcription by Targeting the TFIIIB Complex

机译：PTEN通过靶向TFIIIB复合物抑制RNA聚合酶III依赖性转录

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摘要

PTEN, a tumor suppressor whose function is frequently lost in human cancers, possesses a lipid phosphatase activity that represses phosphatidylinositol 3-kinase (PI3K) signaling, controlling cell growth, proliferation, and survival. The potential for PTEN to regulate the synthesis of RNA polymerase (Pol) III transcription products, including tRNAs and 5S rRNAs, was evaluated. The expression of PTEN in PTEN-deficient cells repressed RNA Pol III transcription, whereas decreased PTEN expression enhanced transcription. Transcription repression by PTEN was uncoupled from PTEN-mediated effects on the cell cycle and was independent of p53. PTEN acts through its lipid phosphatase activity, inhibiting the PI3K/Akt/mTOR/S6K pathway to decrease transcription. PTEN, through the inactivation of mTOR, targets the TFIIIB complex, disrupting the association between TATA-binding protein and Brf1. Kinetic analysis revealed that PTEN initially induces a decrease in the serine phosphorylation of Brf1, leading to a selective reduction in the occupancy of all TFIIIB subunits on tRNALeu genes, whereas prolonged PTEN expression results in the enhanced serine phosphorylation of Bdp1. Together, these results demonstrate a new class of genes regulated by PTEN through its ability to repress the activation of PI3K/Akt/mTOR/S6K signaling.
机译：PTEN是一种在人类癌症中经常丧失功能的肿瘤抑制因子，具有脂质磷酸酶活性，该活性可抑制磷脂酰肌醇3-激酶（PI3K）信号传导，控制细胞的生长，增殖和存活。评估了PTEN调节RNA聚合酶（Pol）III转录产物（包括tRNA和5S rRNA）合成的潜力。 PTEN缺陷细胞中PTEN的表达抑制RNA Pol III转录，而降低的PTEN表达则增强转录。 PTEN的转录抑制与PTEN介导的对细胞周期的作用无关，并且独立于p53。 PTEN通过其脂质磷酸酶活性起作用，抑制PI3K / Akt / mTOR / S6K途径以减少转录。通过失活mTOR，PTEN靶向TFIIIB复合物，破坏TATA结合蛋白与Brf1之间的结合。动力学分析表明，PTEN最初会诱导Brf1的丝氨酸磷酸化降低，从而导致tRNA Leu 基因上所有TFIIIB亚基的占有率选择性降低，而PTEN的延长表达会导致丝氨酸磷酸化增强。 Bdp1。总之，这些结果证明了PTEN通过抑制PI3K / Akt / mTOR / S6K信号传导的激活而调控的一类新基因。

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