ArticleThe Journal of biological chemistry2013
The HECT type ubiquitin ligase NEDL2 is degraded by anaphase-promoting complex/cyclosome (APC/C)-Cdh1, and its tight regulation maintains the metaphase to anaphase transition.
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 26 papers.
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Who cites it
26 citing papers in PubMed, 46 citations in OpenAlex.
- Amyloid Precursor Protein Processing Links Female Urgency Urinary Incontinence with Alzheimer's Disease: Implications for Treatment.International journal of molecular sciences · 2026Article
- USP14 modulates stem-like properties, tumorigenicity, and radiotherapy resistance in glioblastoma stem cells through stabilization of MST4-phosphorylated ALKBH5.Theranostics · 2025Article
- E3 ubiquitin ligase HECW2: a promising target for tumour therapy.Cancer cell international · 2024Review
- The GATOR2 complex maintains lysosomal-autophagic function by inhibiting the protein degradation of MiT/TFEs.Molecular cell · 2024Article
- Identification and validation of shared gene signature of kidney renal clear cell carcinoma and COVID-19.PeerJ · 2024Article
- The Role of HECT E3 Ubiquitin Ligases in Colorectal Cancer.Biomedicines · 2023Review
- HECW2 promotes the progression and chemoresistance of colorectal cancer via AKT/mTOR signaling activation by mediating the ubiquitin-proteasome degradation of lamin B1.Journal of Cancer · 2023Article
- Unraveling the Potential Role of NEDD4-like E3 Ligases in Cancer.International journal of molecular sciences · 2022Review
- De novo FZR1 loss-of-function variants cause developmental and epileptic encephalopathies.Brain : a journal of neurology · 2022Article
- The Roles of NEDD4 Subfamily of HECT E3 Ubiquitin Ligases in Neurodevelopment and Neurodegeneration.International journal of molecular sciences · 2022Review
- Analysis of circRNA and miRNA expression profiles in IGF3-induced ovarian maturation in spotted scat (Frontiers in endocrinology · 2022Article
- DRG1 Maintains Intestinal Epithelial Cell Junctions and Barrier Function by Regulating RAC1 Activity in Necrotizing Enterocolitis.Digestive diseases and sciences · 2021Article
- The p53 family member p73 in the regulation of cell stress response.Biology direct · 2021Review
- Clinicopathological and Genomic Characterization of a Simmental Calf with Generalized Bovine Juvenile Angiomatosis.Animals : an open access journal from MDPI · 2021Article
- NEDD4-like ubiquitin ligase 2 protein (NEDL2) in porcine spermatozoa, oocytes, and preimplantation embryos and its role in oocyte fertilization†.Biology of reproduction · 2021Article
- Neurodevelopmental Disorders (NDD) Caused by Genomic Alterations of the Ubiquitin-Proteasome System (UPS): the Possible Contribution of Immune Dysregulation to Disease Pathogenesis.Frontiers in molecular neuroscience · 2021Review
- Identification of a Ubiquitin Related Genes Signature for Predicting Prognosis of Prostate Cancer.Frontiers in genetics · 2021Article
- Review
- Overexpression of the HECT ubiquitin ligase PfUT prolongs the intraerythrocytic cycle and reduces invasion efficiency of Plasmodium falciparum.Scientific reports · 2019Article
- Loss of the neurodevelopmental gene Zswim6 alters striatal morphology and motor regulation.Neurobiology of disease · 2017Article
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
NEDD4-like ubiquitin ligase 2 (NEDL2) is a HECT type ubiquitin ligase. NEDL2 enhances p73 transcriptional activity and degrades ATR kinase in lamin misexpressed cells. Compared with the important functions of other HECT type ubiquitin ligase, there is less study concerning the function and regulation of NEDL2. Using primary antibody immunoprecipitation and mass spectrometry, we identify a list of potential proteins that are putative NEDL2-interacting proteins. The candidate list contains many of mitotic proteins, especially including several subunits of anaphase-promoting complex/cyclosome (APC/C) and Cdh1, an activator of APC/C. Cdh1 can interact with NEDL2 in vivo and in vitro. Cdh1 recognizes one of the NEDL2 destruction boxes (R(740)GSL(743)) and targets it for degradation in an APC/C-dependent manner during mitotic exit. Overexpression of Cdh1 reduces the protein level of NEDL2, whereas knockdown of Cdh1 increases the protein level of NEDL2 but has no effect on the NEDL2 mRNA level. NEDL2 associates with mitotic spindles, and its protein level reaches a maximum in mitosis. The function of NEDL2 during mitosis is essential because NEDL2 depletion prolongs metaphase, and overexpression of NEDL2 induces chromosomal lagging. Elevated expression of NEDL2 protein and mRNA are both found in colon cancer and cervix cancer. We conclude that NEDL2 is a novel substrate of APC/C-Cdh1 as cells exit mitosis and functions as a regulator of the metaphase to anaphase transition. Its overexpression may contribute to tumorigenesis.
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