ArticleJournal of cellular and molecular medicine2018
NEDD4-induced degradative ubiquitination of phosphatidylinositol 4-phosphate 5-kinase α and its implication in breast cancer cell proliferation.
Article in Journal of cellular and molecular medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 25 citations in OpenAlex.
- PIP5K3 upregulation correlates with unfavorable prognosis in patients with nasopharyngeal carcinoma.Histology and histopathology · 2026Article
- Implicates of PIP5K1α in asthma-related biological processes: insights into mechanisms and therapeutic potential.Journal of translational medicine · 2025Review
- Phosphoinositide kinases in cancer: from molecular mechanisms to therapeutic opportunities.Nature reviews. Cancer · 2025Review
- NEDD4 signaling: a new frontier in the diagnosis and treatment of breast and ovarian cancers.Medical oncology (Northwood, London, England) · 2025Review
- Role and therapeutic potential of the NEDD4 family in breast cancer.Frontiers in pharmacology · 2025Review
- Ubiquitin ligase NEDD4 promotes the proliferation of hepatocellular carcinoma cells through targeting PCDH17 protein for ubiquitination and degradation.The Journal of biological chemistry · 2024Article
- PIP5Kγ Mediates PI(4,5)P2/Merlin/LATS1 Signaling Activation and Interplays with Hsc70 in Hippo-YAP Pathway Regulation.International journal of molecular sciences · 2023Article
- Lipid kinase PIP5Kα contributes to Hippo pathway activation via interaction with Merlin and by mediating plasma membrane targeting of LATS1.Cell communication and signaling : CCS · 2023Article
- Lipid kinases PIP5Ks and PIP4Ks: potential drug targets for breast cancer.Frontiers in oncology · 2023Review
- PIP kinases: A versatile family that demands further therapeutic attention.Advances in biological regulation · 2023Article
- Unraveling the Potential Role of NEDD4-like E3 Ligases in Cancer.International journal of molecular sciences · 2022Review
- Article
- NEDD4 Induces K48-Linked Degradative Ubiquitination of Hepatitis B Virus X Protein and Inhibits HBV-Associated HCC Progression.Frontiers in oncology · 2021Article
- Honokiol ameliorates angiotensin II-induced hypertension and endothelial dysfunction by inhibiting HDAC6-mediated cystathionine γ-lyase degradation.Journal of cellular and molecular medicine · 2020Article
- Identification of prognostic biomarkers and drug target prediction for colon cancer according to a competitive endogenous RNA network.Molecular medicine reports · 2020Article
- NEDD4 expression is associated with breast cancer progression and is predictive of a poor prognosis.Breast cancer research : BCR · 2019Article
- NEDD4-induced degradative ubiquitination of phosphatidylinositol 4-phosphate 5-kinase α and its implication in breast cancer cell proliferation.Journal of cellular and molecular medicine · 2018Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Phosphatidylinositol 4-phosphate 5-kinase (PIP5K) family members generate phosphatidylinositol 4,5-bisphosphate (PIP2), a critical lipid regulator of diverse physiological processes. The PIP5K-dependent PIP2 generation can also act upstream of the oncogenic phosphatidylinositol 3-kinase (PI3K)/Akt pathway. Many studies have demonstrated various mechanisms of spatiotemporal regulation of PIP5K catalytic activity. However, there are few studies on regulation of PIP5K protein stability. Here, we examined potential regulation of PIP5Kα, a PIP5K isoform, via ubiquitin-proteasome system, and its implication for breast cancer. Our results showed that the ubiquitin ligase NEDD4 (neural precursor cell expressed, developmentally down-regulated gene 4) mediated ubiquitination and proteasomal degradation of PIP5Kα, consequently reducing plasma membrane PIP2 level. NEDD4 interacted with the C-terminal region and ubiquitinated the N-terminal lysine 88 in PIP5Kα. In addition, PIP5Kα gene disruption inhibited epidermal growth factor (EGF)-induced Akt activation and caused significant proliferation defect in breast cancer cells. Notably, PIP5Kα K88R mutant that was resistant to NEDD4-mediated ubiquitination and degradation showed more potentiating effects on Akt activation by EGF and cell proliferation than wild-type PIP5Kα. Collectively, these results suggest that PIP5Kα is a novel degradative substrate of NEDD4 and that the PIP5Kα-dependent PIP2 pool contributing to breast cancer cell proliferation through PI3K/Akt activation is negatively controlled by NEDD4.
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