1. Главная
  2. Ресурсы
  3. Библиотечный поиск
Transcription factorNFE2L2/NRF2 is aregulator ofmacroautophagy genes Marta PajaresNatalia Jiménez-MorenoÁngel J. García‐Yagüe2016 год

Transcription factor NFE2L2/NRF2 is a regulator of macroautophagy genes
статья из журнала

Полный текстСтраница публикацииПубликация в OpenAlex
Аннотация: Autophagy is a highly coordinated process that is controlled at several levels including transcriptional regulation. Here, we identify the transcription factor NFE2L2/NRF2 (nuclear factor, erythroid 2 like 2) as a regulator of autophagy gene expression and its relevance in a mouse model of Alzheimer disease (AD) that reproduces impaired APP (amyloid β precursor protein) and human (Hs)MAPT/TAU processing, clearance and aggregation. We screened the chromatin immunoprecipitation database ENCODE for 2 proteins, MAFK and BACH1, that bind the NFE2L2-regulated enhancer antioxidant response element (ARE). Using a script generated from the JASPAR's consensus ARE sequence, we identified 27 putative AREs in 16 autophagy-related genes. Twelve of these sequences were validated as NFE2L2 regulated AREs in 9 autophagy genes by additional ChIP assays and quantitative RT-PCR on human and mouse cells after NFE2L2 activation with sulforaphane. Mouse embryo fibroblasts of nfe2l2-knockout mice exhibited reduced expression of autophagy genes, which was rescued by an NFE2L2 expressing lentivirus, and impaired autophagy flux when exposed to hydrogen peroxide. NFE2L2-deficient mice co-expressing HsAPPV717I and HsMAPTP301L, exhibited more intracellular aggregates of these proteins and reduced neuronal levels of SQSTM1/p62, CALCOCO2/NDP52, ULK1, ATG5 and GABARAPL1. Also, colocalization of HsAPPV717I and HsMAPTP301L with the NFE2L2-regulated autophagy marker SQSTM1/p62 was reduced in the absence of NFE2L2. In AD patients, neurons expressing high levels of APP or MAPT also expressed SQSTM1/p62 and nuclear NFE2L2, suggesting their attempt to degrade intraneuronal aggregates through autophagy. This study shows that NFE2L2 modulates autophagy gene expression and suggests a new strategy to combat proteinopathies.
Год издания: 2016
Авторы: Marta Pajares, Natalia Jiménez-Moreno, Ángel J. García‐Yagüe, Maribel Escoll, Marı́a L. de Ceballos, Fred Van Leuven, Alberto Rábano, Masayuki Yamamoto, Ana I. Rojo, Antonio Cuadrado
Издательство: Taylor & Francis
Источник: Autophagy
Ключевые слова: Genomics, phytochemicals, and oxidative stress, Autophagy in Disease and Therapy, Nuclear Receptors and Signaling
Другие ссылки: Autophagy (PDF)
Autophagy (HTML)
Europe PMC (PubMed Central) (PDF)
Europe PMC (PubMed Central) (HTML)
Bristol Research (University of Bristol) (PDF)
Bristol Research (University of Bristol) (HTML)
LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (PDF)
LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (HTML)
Bristol Research (University of Bristol) (HTML)
PubMed Central (HTML)
PubMed (HTML)