ArticleJournal of cell science2013
Ubiquitylation of phosphatidylinositol 4-phosphate 5-kinase type I γ by HECTD1 regulates focal adhesion dynamics and cell migration.
Article in Journal of cell science, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 63 citations in OpenAlex.
- Nuclear ubiquitination permits Hippo-YAP signal for liver development and tumorigenesis.Nature chemical biology · 2025Article
- Phosphoinositide kinases in cancer: from molecular mechanisms to therapeutic opportunities.Nature reviews. Cancer · 2025Review
- Talin2 binds to non-muscle myosin IIa and regulates cell attachment and fibronectin secretion.Scientific reports · 2024Article
- Pip5k1c expression in osteocytes regulates bone remodeling in mice.Journal of orthopaedic translation · 2024Article
- Identification and functional analysis of rare HECTD1 missense variants in human neural tube defects.Human genetics · 2024Article
- The 'Other' subfamily of HECT E3 ubiquitin ligases evaluate the tumour immune microenvironment and prognosis in patients with hepatocellular carcinoma.IET systems biology · 2024Article
- A Novel Natural Killer Cell-related Gene Signature for Improving the Prediction of Prognosis and Immunotherapy Response in Bladder Cancer.Combinatorial chemistry & high throughput screening · 2024Article
- MiR-4649-5p acts as a tumor-suppressive microRNA in triple negative breast cancer by direct interaction with PIP5K1C, thereby potentiating growth-inhibitory effects of the AKT inhibitor capivasertib.Breast cancer research : BCR · 2023Article
- Lipid kinases PIP5Ks and PIP4Ks: potential drug targets for breast cancer.Frontiers in oncology · 2023Review
- CircRNA-miRNA interactions in atherogenesis.Molecular and cellular biochemistry · 2022Review
- The E3 ubiquitin ligase HECTD1 contributes to cell proliferation through an effect on mitosis.Scientific reports · 2022Article
- Proteasomal turnover of the RhoGAP tumor suppressor DLC1 is regulated by HECTD1 and USP7.Scientific reports · 2022Article
- Adipocyte-specific deletion of PIP5K1c reduces diet-induced obesity and insulin resistance by increasing energy expenditure.Lipids in health and disease · 2022Article
- Low HECTD1 mRNA expression is associated with poor prognosis and may be correlated with increased mitochondrial respiratory function in breast cancer.American journal of cancer research · 2022Article
- Involvement of HECTD1 in LPS-induced astrocyte activation via σ-1R-JNK/p38-FOXJ2 axis.Cell & bioscience · 2021Article
- A distinct talin2 structure directs isoform specificity in cell adhesion.The Journal of biological chemistry · 2020Article
- Modeling and analysis of Hi-C data by HiSIF identifies characteristic promoter-distal loops.Genome medicine · 2020Article
- circDLPAG4/HECTD1 mediates ischaemia/reperfusion injury in endothelial cells via ER stress.RNA biology · 2020Article
- Novel genetic variants ofAmerican journal of cancer research · 2020Article
- The ubiquitin ligase HECTD1 promotes retinoic acid signaling required for development of the aortic arch.Disease models & mechanisms · 2019Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Phosphatidylinositol 4-phosphate 5-kinase type I γ (PIPKIγ90) binds talin and localizes at focal adhesions (FAs). Phosphatidylinositol (4,5)-bisphosphate (PIP2) generated by PIPKIγ90 is essential for FA formation and cell migration. On the other hand, PIPKIγ90 and the β-integrin tail compete for overlapping binding sites on talin. Enhanced PIPKIγ90-talin interaction suppresses talin binding to the β-integrin. It is unknown how PIPKIγ90 is removed from the PIPKIγ90-talin complex after on-site PIP2 production during cell migration. Here we show that PIPKIγ90 is a substrate for HECTD1, an E3 ubiquitin ligase regulating cell migration. HECTD1 ubiquitinated PIPKIγ90 at lysine 97 and resulted in PIPKIγ90 degradation. Expression of the mutant PIPKIγ90(K97R) enhanced PIP2 and PIP3 production, inhibited FA assembly and disassembly and inhibited cancer cell migration, invasion and metastasis. Interestingly, mutation at tryptophan 647 abolished the inhibition of PIPKIγ90(K97R) on FA dynamics and partially rescued cancer cell migration and invasion. Thus, cycling PIPKIγ90 ubiquitylation by HECTD1 and consequent degradation remove PIPKIγ90 from talin after on-site PIP2 production, providing an essential regulatory mechanism for FA dynamics and cell migration.
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Registered trials
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.