ArticlePloS one2013
WWP1 E3 ligase targets LATS1 for ubiquitin-mediated degradation in breast cancer cells.
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 58 papers.
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Who cites it
58 citing papers in PubMed, 93 citations in OpenAlex.
- E2F-mediated activation of mTORC1 through the ubiquitin-proteasome system promotes lung adenocarcinoma progression.Cell death & disease · 2026Article
- piR-27222 alleviates dexamethasone-induced osteoporosis by inhibiting ferroptosis through modulating WWP1.Journal of orthopaedic surgery and research · 2026Article
- HCV infection induces ubiquitin-dependent degradation of LATS1, inactivating the Hippo pathway and upregulating transcription of the CYR61 and CTGF genes.The Journal of general virology · 2026Article
- E3 ubiquitin ligases: structural diversity, dysregulation in disease, and their emerging role in targeted therapeutic strategies.Frontiers in molecular biosciences · 2026Review
- Targeting WWPI HECT Domain by Small Inhibitors for Restoring PTEN Tumor Suppressive Role in Glioblastoma Therapy.Anti-cancer agents in medicinal chemistry · 2026Article
- Role and therapeutic potential of the NEDD4 family in breast cancer.Frontiers in pharmacology · 2025Review
- GPRC5A promotes lung colonization of esophageal squamous cell carcinoma.Nature communications · 2024Article
- Portrait of WWP1: the current state in human cancer.Frontiers in cell and developmental biology · 2024Review
- WWP1 E3 ligase at the crossroads of health and disease.Cell death & disease · 2023Review
- UBE4B interacts with the ITCH E3 ubiquitin ligase to induce Ku70 and c-FLIPL polyubiquitination and enhanced neuroblastoma apoptosis.Cell death & disease · 2023Article
- The Ubiquitin-Proteasome System in Tumor Metabolism.Cancers · 2023Review
- WWP2 drives the progression of gastric cancer by facilitating the ubiquitination and degradation of LATS1 protein.Cell communication and signaling : CCS · 2023Article
- Unraveling the Potential Role of NEDD4-like E3 Ligases in Cancer.International journal of molecular sciences · 2022Review
- Targeting the Hippo pathway in heart repair.Cardiovascular research · 2022Review
- The clinicopathological and prognostic significances of LATS1 expression in breast cancer.Histology and histopathology · 2022Article
- Review
- Review
- PRAMEF2-mediated dynamic regulation of YAP signaling promotes tumorigenesis.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- AMOTL2 mono-ubiquitination by WWP1 promotes contact inhibition by facilitating LATS activation.Life science alliance · 2021Article
- The emerging role of WWP1 in cancer development and progression.Cell death discovery · 2021Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
The Large Tumor Suppressor 1 (LATS1) is a serine/threonine kinase and tumor suppressor found down-regulated in various human cancers. LATS1 has recently been identified as a central player of the emerging Hippo signaling pathway, which plays important roles in organ size control, tumorigenesis, and stem cell differentiation and renewal, etc. Although mounting evidence supports a role of LATS1 in tumor suppression and tumorigenesis, how LATS1 is regulated at the molecular level is not fully understood. Recently several positive regulators of LATS1 (Mst1/2, MOB1, Kibra, etc) have been identified but how LATS1 is negatively regulated is still largely unknown. We have recently identified Itch, a member of the NEDD4-like family E3 ubiquitin ligases, as a novel negative regulator of LATS1. However, whether other ubiquitin ligases modulate LATS1 stability and function is unclear. By screening many E3 ligases of the NEDD4-like family using over-expression and short-interference RNA knockdown approaches, we have identified WWP1 E3 ligase as another novel negative regulator of LATS1. We have provided in vitro and in vivo evidence that WWP1 is essential for LATS1 stability and negatively regulate LATS1 by promoting LATS1 degradation through polyubiquitination and the 26S proteasome pathway. Importantly, we also showed that degradation of LATS1 is critical in mediating WWP1-induced increased cell proliferation in breast cancer cells. Since WWP1 is an oncogene and LATS1 is a tumor suppressor gene in breast cancer, our studies provide a promising therapeutic strategy in which developed drugs targeting WWP1 cause activation of LATS1 in suppressing breast cancer cell growth.
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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.