XBP1 mRNA Splicing Triggers an Autophagic Response in Endothelial Cells through BECLIN-1 Transcriptional Activation

Margariti, Andriani; Li, Hongling; Chen, Ting; Martin, Daniel; Vizcay‐Barrena, Gema; Alam, Saydul; Karamariti, Eirini; Xiao, Qingzhong; Zampetaki, Anna; Zhang, Zhongyi; Wang, Wen; Jiang, Zhixin; Gao, Chan; Ma, Benyu; Chen, Ye-Guang; Cockerill, Gillian; Hu, Yanhua; Xu, Qingbo; Zeng, Lingfang

doi:10.1074/jbc.m112.412783

Cited by 235 publications

(176 citation statements)

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“…The transcription factor X-box-binding protein 1 (XBP1) is another crucial regulator of FOXO1 activation and degradation. In addition, spliced XBP1 can directly bind to the promoter region of BECN1 thus acting as an autophagy activator or inhibitor depending on the splice isoform (Margariti et al, 2013). Unlike TFEB, FOXO1 also acts as an autophagy inducer within the cytosol by directly binding to autophagy-related proteins (Zhao et al, 2010).…”

Section: The Foxo Family -Location Mattersmentioning

confidence: 99%

Transcriptional regulation of mammalian autophagy at a glance

Füllgrabe

Ghislat

Cho

et al. 2016

Journal of Cell Science

169

171

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Macroautophagy, hereafter referred to as autophagy, is a catabolic process that results in the lysosomal degradation of cytoplasmic contents ranging from abnormal proteins to damaged cell organelles. It is activated under diverse conditions, including nutrient deprivation and hypoxia. During autophagy, members of the core autophagy-related (ATG) family of proteins mediate membrane rearrangements, which lead to the engulfment and degradation of cytoplasmic cargo. Recently, the nuclear regulation of autophagy, especially by transcription factors and histone modifiers, has gained increased attention. These factors are not only involved in rapid responses to autophagic stimuli, but also regulate the long-term outcome of autophagy. Now there are more than 20 transcription factors that have been shown to be linked to the autophagic process. However, their interplay and timing appear enigmatic as several have been individually shown to act as major regulators of autophagy. This Cell Science at a Glance article and the accompanying poster highlights the main cellular regulators of transcription involved in mammalian autophagy and their target genes.

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Section: The Foxo Family -Location Mattersmentioning

confidence: 99%

Transcriptional regulation of mammalian autophagy at a glance

Füllgrabe

Ghislat

Cho

et al. 2016

Journal of Cell Science

169

171

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“…Splicing of the mRNA of X-box-binding protein 1, which is an important event during ER stress, allows formation of a potent transcription factor in ECs that triggers an autophagic response through transcriptional activation of the autophagy regulator Beclin 1. 30 Because silencing of Beclin 1 in ECs reduces the proportion of annexin V staining but not oxLDLinduced apoptosis, activation of endothelial autophagy by oxLDL seems to occur independent of ER stress and downstream apoptotic signaling. Instead, the autophagic program in oxLDL-exposed ECs is considered to be involved in the externalization of phosphatidylserine as an eat-me-signal for optimal clearance of dead cells.…”

Section: Autophagy In the Normal Vessel Wall Autophagy Is A Cytoprotementioning

confidence: 99%

Autophagy in Vascular Disease

Meyer

Grootaert

Michiels

et al. 2015

Circulation Research

239

179

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A utophagy is a complex intracellular process that delivers cytoplasmic constituents for degradation into lysosomes.1,2 Three main types of autophagy have been described: (1) microautophagy, comprising direct engulfment of cytoplasmic material by lysosomes via inward invaginations of the lysosomal membrane, (2) macroautophagy, characterized by formation of double-membrane sequestering compartments termed autophagosomes that fuse with lysosomes for delivery of cytoplasmic cargo, and (3) chaperone-mediated autophagy, mediated by a chaperone complex and lysosomal-associated membrane protein type 2A to degrade cytosolic proteins with a specific targeting motif. The term autophagy usually refers to macroautophagy, which is the most prevalent and beststudied form of autophagy. Also in this review, we will focus exclusively on macroautophagy, further cited as autophagy.Autophagy occurs at basal levels in most tissues to allow constitutive turnover of cytosolic components but is stimulated by environmental stress-related signals (eg, nutrient deprivation and oxidative injury) to recycle nutrients and to generate energy for maintenance of cell viability in unfavorable conditions.1 In addition to cellular stress, basal autophagy can be intensified by specific drugs, 3 indicating that the autophagic machinery is a potential therapeutic target for diverse diseases. Indeed, given that autophagy is involved in the prevention

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“…However, phospho-JNK protein levels were unaffected by B-I09 treatment ( Supplemental Figure 5A). Additionally, XBP1s can regulate the expression of BECN1, thereby inducing autophagy (29,30), which confers a cytoprotective advantage in c-Myc-overexpressing mammalian (10) and Drosophila (11) cells. However, autophagy (based on p62 and LC3-II abundance) was not suppressed by B-I09 treatment (Supplemental Figure 5B), indicating no decline in autophagic flux in this setting.…”

Section: B-i09 Suppresses Growth and Induces Apoptosis In Human And Mmentioning

confidence: 99%