期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 108, 期 52, 页码 21093-21098出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1112061109
关键词
cell death; neurodegeneration; Alzheimer disease
资金
- Medical Research Council, United Kingdom
- Odysseus
- VIB, Belgium
- Alleanza Contro il Cancro [ACC12]
- Ministero dell'Istruzione, dell'Universite della Ricerca/Progetti di Ricerca d'Interesse Nazionale/Fondo per gli Investimenti della Ricerca di Base [RBIP06LCA9_0023, RBIP06LCA9_0C]
- Associazione Italiana per la Ricerca sul Cancro [2008-2010_33-08, 5471, 2011-IG11955]
- AIRC [9979]
- Italian Human ProteomeNet [RBRN07BMCT]
- Ministry of Health [26/07]
- Istituto Dermopatico dell'Immacolata-Istituto di Ricovero e Cura a Carattere Scientifico
- Ministry of Education and Science of the Russian Federation [11.G34.31.0069]
- Medical Research Council [MC_U132670600] Funding Source: researchfish
- MRC [MC_U132670600] Funding Source: UKRI
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.
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