ArticlePloS one2013
The short isoform of the ubiquitin ligase NEDD4L is a CREB target gene in hepatocytes.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 23 citations in OpenAlex.
- NEDD4L knockdown reduced lipid accumulation in non-alcoholic fatty liver disease by promoting the activity of PI3K/AKT signaling pathway.European journal of medical research · 2025Article
- Promoting proteostasis by cAMP/PKA and cGMP/PKG.Trends in molecular medicine · 2025Review
- NEDD4L mediates ITGB4 ubiquitination and degradation to suppress esophageal carcinoma progression.Cell communication and signaling : CCS · 2024Article
- p21-activated kinase 4 controls the aggregation of α-synuclein by reducing the monomeric and aggregated forms of α-synuclein: involvement of the E3 ubiquitin ligase NEDD4-1.Cell death & disease · 2022Article
- Downregulation of NEDD4L by EGFR signaling promotes the development of lung adenocarcinoma.Journal of translational medicine · 2022Article
- Hepatocyte-specific Nrf2 deficiency mitigates high-fat diet-induced hepatic steatosis: Involvement of reduced PPARγ expression.Redox biology · 2020Article
- C2-lacking isoform of Nedd4-2 regulates excitatory synaptic strength through GluA1 ubiquitination-independent mechanisms.Journal of neurochemistry · 2019Article
- Gs-DREADD Knock-In Mice for Tissue-Specific, Temporal Stimulation of Cyclic AMP Signaling.Molecular and cellular biology · 2017Article
- The E3 ubiquitin ligase Nedd4/Nedd4L is directly regulated by microRNA 1.Development (Cambridge, England) · 2017Article
- MicroRNA-122 regulates polyploidization in the murine liver.Hepatology (Baltimore, Md.) · 2016Article
- Gs-coupled GPCR signalling in AgRP neurons triggers sustained increase in food intake.Nature communications · 2016Article
- Article
- Skeletal muscle salt inducible kinase 1 promotes insulin resistance in obesity.Molecular metabolism · 2016Article
- Cyclic AMP signaling reduces sirtuin 6 expression in non-small cell lung cancer cells by promoting ubiquitin-proteasomal degradation via inhibition of the Raf-MEK-ERK (Raf/mitogen-activated extracellular signal-regulated kinase/extracellular signal-regulated kinase) pathway.The Journal of biological chemistry · 2015Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
During cycles of fasting and feeding, liver function is regulated by both transcriptional and post-translational events. Regulated protein degradation has recently emerged as a key mechanism to control abundance of specific hepatic proteins under different nutritional conditions. As glucagon signaling through cAMP and PKA is central to glucose output during fasting, we hypothesized that this signaling pathway may also regulate ubiquitin ligases in the fasted state. Here we show that fasting stimuli promote expression of the short isoform of the E3 ubiquitin ligase Nedd4l in primary mouse hepatocytes. Nedd4l-short mRNA and NEDD4L (short isoform) protein accumulate in glucagon-treated primary mouse hepatocytes and in liver tissues during fasting. We identified a functional cAMP response element in the alternate Nedd4l-short promoter; mutation of this element blunts cAMP-induced expression of a Nedd4l reporter construct. CREB occupies the endogenous Nedd4l locus near this element. CREB and its co-activator CRTC2, both activated by fasting stimuli, contribute to glucagon-stimulated Nedd4l-short expression in primary hepatocytes. siRNA-mediated Nedd4l depletion in primary hepatocytes did not affect gluconeogenic gene expression, glucose output or glycogen synthesis. Our findings reveal a new mechanism of Nedd4l transcriptional regulation in liver cells.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.