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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Neuronal differentiation by TAp73 is mediated by microRNA-34a regulation of synaptic protein targets
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Neuronal differentiation by TAp73 is mediated by microRNA-34a regulation of synaptic protein targets

机译：TAp73的神经元分化是由microRNA-34a调节突触蛋白靶标介导的

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摘要

The p53-family member TAp73 is a transcription factor that plays a key role in many biological processes. Here, we show that p73 drives the expression of microRNA (miR)-34a, but not miR-34b and -c, by acting on specific binding sites on the miR-34a promoter. Expression of miR-34a is modulated in parallel with that of TAp73 during in vitro differentiation of neuroblastoma cells and cortical neurons. Retinoid-driven neuroblastoma differentiation is inhibited by knockdown of either p73 or miR-34a. Transcript expression of miR-34a is significantly reduced in vivo both in the cortex and hippocampus of p73~(-/-) mice; miR-34a and TAp73 expression also increase during postnatal development of the brain and cerebellum when synaptogenesis occurs. Accordingly, overexpression or silencing of miR-34a inversely modulates expression of synaptic targets, including synaptotagmin-1 and syntaxin-1A. Notably, the axis TAp73/miR-34a/synaptotagmin-1 is conserved in brains from Alzheimer's patients. These data reinforce a role for TAp73 in neuronal development.
机译：p53家族成员TAp73是在许多生物学过程中起关键作用的转录因子。在这里，我们显示p73通过作用于miR-34a启动子上的特异性结合位点来驱动microRNA（miR）-34a的表达，但不驱动miR-34b和-c的表达。在成神经细胞瘤细胞和皮层神经元的体外分化过程中，miR-34a的表达与TAp73的表达平行调节。抑制p73或miR-34a抑制类维生素A驱动的神经母细胞瘤的分化。在p73〜（-/-）小鼠的皮层和海马中，miR-34a的转录表达在体内均显着降低。当发生突触发生时，在大脑和小脑的出生后发育过程中，miR-34a和TAp73的表达也会增加。因此，miR-34a的过表达或沉默反过来调节突触靶标的表达，包括突触标记素-1和syntaxin-1A。值得注意的是，轴TAp73 / miR-34a / synaptotagmin-1在阿尔茨海默氏病患者的大脑中是保守的。这些数据加强了TAp73在神经元发育中的作用。

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    Massimiliano Agostini; Paola Tucci; Richard Killick; Eleonora Candi; Berna S. Sayan; Pia Rivetti di val Cervo; Pierluigi Nicotera; Frank McKeon; Richard A. Knight; Tak W. Mak; Gerry Melino;

  • 作者单位

    Toxicology Unit, Medical Research Council, Leicester University, Leicester LE1 9HN, United Kingdom;

    Biochemistry Laboratory, Istituto Dermopatico deH'Immacolata-lstituto di Ricovero e Cura a Carattere Scientifico and University of Rome "Tor Vergata", 00133 Rome, Italy,Department of Pharmaco-Biology, University of Calabria, 87036 Rende (CS), Italy;

    Kings College Institute of Psychiatry, Old Age Psychiatry and Dementia, London SE5 8AF, United Kingdom;

    Biochemistry Laboratory, Istituto Dermopatico deH'Immacolata-lstituto di Ricovero e Cura a Carattere Scientifico and University of Rome "Tor Vergata", 00133 Rome, Italy;

    Toxicology Unit, Medical Research Council, Leicester University, Leicester LE1 9HN, United Kingdom;

    Biochemistry Laboratory, Istituto Dermopatico deH'Immacolata-lstituto di Ricovero e Cura a Carattere Scientifico and University of Rome "Tor Vergata", 00133 Rome, Italy;

    Deutsche Zentrum fuer Neurodegenerative Erkrankungen, 53175 Bonn, Germany;

    Department of Cell Biology, Harvard Medical School, Boston, MA 02115;

    Toxicology Unit, Medical Research Council, Leicester University, Leicester LE1 9HN, United Kingdom;

    The Campbell Family Institute for Breast Cancer Research, Princess Margaret Hospital, Toronto, ON, Canada M5G 2C1;

    Toxicology Unit, Medical Research Council, Leicester University, Leicester LE1 9HN, United Kingdom,Biochemistry Laboratory, Istituto Dermopatico deH'Immacolata-lstituto di Ricovero e Cura a Carattere Scientifico and University of Rome "Tor Vergata", 00133 Rome, Italy;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
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  • 关键词

    cell death; neurodegeneration; alzheimer disease;

    机译：细胞死亡;神经变性老年痴呆症;

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