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Endoplasmic reticulum stress up‐regulates Nedd4‐2 to induce autophagy

Overview of attention for article published in FASEB Journal, March 2016
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Title
Endoplasmic reticulum stress up‐regulates Nedd4‐2 to induce autophagy
Published in
FASEB Journal, March 2016
DOI 10.1096/fj.201500119
Pubmed ID
Authors

Hao Wang, Ruo‐Qiong Sun, Daria Camera, Xiao‐Yi Zeng, Eunjung Jo, Stanley M. H. Chan, Terence P. Herbert, Juan C. Molero, Ji‐Ming Ye

Abstract

The accumulation of unfolded proteins within the endoplasmic reticulum (ER) causes ER stress and activation of unfolded protein response (UPR). This response can trigger ER-associated degradation and autophagy, which clear unfolded proteins and restore protein homeostasis. Recently, it has become clear that ubiquitination plays an important role in the regulation of autophagy. In the present study, we investigated how the E3 ubiquitin ligase Nedd4-2 (neural precursor cell expressed developmentally down-regulated protein 4-2) interacts with ER stress and autophagy. In mice, we found that an increase in the expression of Nedd4-2, which was concomitant with the activation of the UPR and autophagy, was caused by a prolonged high-fructose and high-fat diet that induces ER stress in the liver. Pharmacologic induction of ER stress also led to an increase in Nedd4-2 expression in cultured cells, which was coincident with UPR and autophagy activation. The inhibition of inositol-requiring enzyme 1 significantly suppressed Nedd4-2 expression. Moreover, increased Nedd4-2 expressionin vivowas closely associated with the activation of inositol-requiring enzyme 1 and increased expression of the spliced form of X-box binding protein 1. Furthermore, knockdown of Nedd4-2 in cultured cells suppressed both basal autophagy and ER stress-induced autophagy, whereas overexpression of Nedd4-2 induced autophagy. Taken together, our findings provide evidence that Nedd4-2 is up-regulated in response to ER stress by the spliced form of X-box binding protein 1 and that this is important in the induction of an appropriate autophagic response.-Wang, H. Sun, R.-Q., Camera, D., Zeng, X.-Y., Jo, E., Chan, S. M. H., Herbert, T. P., Molero, J. C, Ye, J.-M. Endoplasmic reticulum stress up-regulates Nedd4-2 to induce autophagy.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 27 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Korea, Republic of 1 4%
Unknown 26 96%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 9 33%
Student > Bachelor 6 22%
Student > Doctoral Student 4 15%
Researcher 2 7%
Professor > Associate Professor 1 4%
Other 1 4%
Unknown 4 15%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 7 26%
Agricultural and Biological Sciences 7 26%
Medicine and Dentistry 5 19%
Neuroscience 2 7%
Chemistry 2 7%
Other 0 0%
Unknown 4 15%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 25 January 2017.
All research outputs
#16,048,009
of 25,374,917 outputs
Outputs from FASEB Journal
#6,960
of 11,449 outputs
Outputs of similar age
#172,752
of 315,687 outputs
Outputs of similar age from FASEB Journal
#72
of 122 outputs
Altmetric has tracked 25,374,917 research outputs across all sources so far. This one is in the 34th percentile – i.e., 34% of other outputs scored the same or lower than it.
So far Altmetric has tracked 11,449 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.5. This one is in the 37th percentile – i.e., 37% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 315,687 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 42nd percentile – i.e., 42% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 122 others from the same source and published within six weeks on either side of this one. This one is in the 37th percentile – i.e., 37% of its contemporaries scored the same or lower than it.