ArticleThe Journal of biological chemistry2013
Ubiquitin-dependent regulation of phospho-AKT dynamics by the ubiquitin E3 ligase, NEDD4-1, in the insulin-like growth factor-1 response.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 1 of them a synthesis that pooled it.
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Who cites it
67 citing papers in PubMed, 1 synthesis or guideline pooled it, 121 citations in OpenAlex.
- Effect of AKT1 (p. E17K) Hotspot Mutation on Malignant Tumorigenesis and Prognosis.Frontiers in cell and developmental biology · 2020Pooled it
- PRAME Augments K63-Linked Ubiquitination and Stabilization of METTL3 to Promote Lung Adenocarcinoma Metastasis.MedComm · 2026Article
- E3 ubiquitin ligase NEDD4 inhibits PEDV infection through ubiquitination and degradation of the viral primase NSP8.Journal of virology · 2026Article
- Inhibition of ZBTB7B-mediated ADPGK transcription by NEDD4 impedes glycolysis and progression of lung adenocarcinoma.Oncogenesis · 2026Article
- The Role of the PI3K/Akt/mTOR Pathway in Atherosclerosis: Mechanisms, Therapeutic Potential, and Emerging Targeted Treatments.Current atherosclerosis reports · 2025Review
- AKT and DUBs: a bidirectional relationship.Cellular & molecular biology letters · 2025Review
- miR-181c-5p/DERL1 pathway controls breast cancer progression mediated by TRAF6-linked K63 ubiquitination of AKT.Cancer cell international · 2024Article
- TRAF6-mediated ubiquitination of AKT in the nucleus is a critical event underlying the desensitization of G protein-coupled receptors.Cell communication and signaling : CCS · 2024Article
- Polyubiquitylated rice stripe virus NS3 translocates to the nucleus to promote cytosolic virus replication via miRNA-induced fibrillin 2 upregulation.PLoS pathogens · 2024Article
- SP1-activated USP27X-AS1 promotes hepatocellular carcinoma progression via USP7-mediated AKT stabilisation.Clinical and translational medicine · 2024Article
- Ubiquitination Links DNA Damage and Repair Signaling to Cancer Metabolism.International journal of molecular sciences · 2023Review
- Targeting pleckstrin-2/Akt signaling reduces proliferation in myeloproliferative neoplasm models.The Journal of clinical investigation · 2023Article
- The role of NEDD4 related HECT-type E3 ubiquitin ligases in defective autophagy in cancer cells: molecular mechanisms and therapeutic perspectives.Molecular medicine (Cambridge, Mass.) · 2023Review
- Targeting the E3 ligase NEDD4 as a novel therapeutic strategy for IGF1 signal pathway-driven gastric cancer.Oncogene · 2023Article
- FKBP51 plays an essential role in Akt ubiquitination that requires Hsp90 and PHLPP.Cell death & disease · 2023Article
- Interfering with the Ubiquitin-Mediated Regulation of Akt as a Strategy for Cancer Treatment.International journal of molecular sciences · 2023Review
- Article
- Review
- The Role of HECT-Type E3 Ligase in the Development of Cardiac Disease.International journal of molecular sciences · 2021Review
- Mutant ASXL1 induces age-related expansion of phenotypic hematopoietic stem cells through activation of Akt/mTOR pathway.Nature communications · 2021Article
7 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
AKT is a critical effector kinase downstream of the PI3K pathway that regulates a plethora of cellular processes including cell growth, death, differentiation, and migration. Mechanisms underlying activated phospho-AKT (pAKT) translocation to its action sites remain unclear. Here we show that NEDD4-1 is a novel E3 ligase that specifically regulates ubiquitin-dependent trafficking of pAKT in insulin-like growth factor (IGF)-1 signaling. NEDD4-1 physically interacts with AKT and promotes HECT domain-dependent ubiquitination of exogenous and endogenous AKT. NEDD4-1 catalyzes K63-type polyubiquitin chain formation on AKT in vitro. Plasma membrane binding is the key step for AKT ubiquitination by NEDD4-1 in vivo. Ubiquitinated pAKT translocates to perinuclear regions, where it is released into the cytoplasm, imported into the nucleus, or coupled with proteasomal degradation. IGF-1 signaling specifically stimulates NEDD4-1-mediated ubiquitination of pAKT, without altering total AKT ubiquitination. A cancer-derived plasma membrane-philic mutant AKT(E17K) is more effectively ubiquitinated by NEDD4-1 and more efficiently trafficked into the nucleus compared with wild type AKT. This study reveals a novel mechanism by which a specific E3 ligase is required for ubiquitin-dependent control of pAKT dynamics in a ligand-specific manner.
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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.