ArticleProceedings of the National Academy of Sciences of the United States of America2013
CRL4A-FBXW5-mediated degradation of DLC1 Rho GTPase-activating protein tumor suppressor promotes non-small cell lung cancer cell growth.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed.
- FBXW5 blunts RIGI/MDA5/IFN signaling to drive immune evasion and chemo-immune resistance in triple-negative breast cancer models.The Journal of clinical investigation · 2026Article
- RRM1 inhibition sensitizes lung adenocarcinoma to decitabine treatment.Cell death & disease · 2026Article
- Filamin a binds deleted in liver cancer 1 (DLC1) to promote its tumor suppressor activity and inhibit the SRF coactivator MRTF-A.Neoplasia (New York, N.Y.) · 2026Article
- The structure and function of FBXW5 in human diseases.Biochemistry and biophysics reports · 2025Review
- Subtype-specific RNA sequencing using micro-dissection revealed extracellular matrix alterations as key factors in lung adenocarcinoma invasion.Translational lung cancer research · 2025Article
- SCFAutophagy · 2024Article
- Individual disruption of 12 testis-enriched genes via the CRISPR/Cas9 system does not affect the fertility of male mice.Journal of reproductive immunology · 2024Article
- DLC1 promotes mechanotransductive feedback for YAP via RhoGAP-mediated focal adhesion turnover.Journal of cell science · 2024Article
- HDAC5 modulates SATB1 transcriptional activity to promote lung adenocarcinoma.British journal of cancer · 2023Article
- Fixing the GAP: The role of RhoGAPs in cancer.European journal of cell biology · 2022Review
- Proteasomal turnover of the RhoGAP tumor suppressor DLC1 is regulated by HECTD1 and USP7.Scientific reports · 2022Article
- The E3 ubiquitin ligase, FBXW5, promotes the migration and invasion of gastric cancer through the dysregulation of the Hippo pathway.Cell death discovery · 2022Article
- Pan-cancer analysis of FBXW family with potential implications in prognosis and immune infiltration.Frontiers in immunology · 2022Article
- Inhibition of cytoplasmic EZH2 induces antitumor activity through stabilization of the DLC1 tumor suppressor protein.Nature communications · 2021Article
- SCFThe EMBO journal · 2021Article
- HOS15 is a transcriptional corepressor of NPR1-mediated gene activation of plant immunity.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Article
- The Role of Cullin-RING Ligases in Striated Muscle Development, Function, and Disease.International journal of molecular sciences · 2020Review
- Cancer-Associated Point Mutations in theCancer research · 2020Article
- ARHGAP24 inhibits cell proliferation and cell cycle progression and induces apoptosis of lung cancer via a STAT6-WWP2-p27 axis.Carcinogenesis · 2020Article
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Authors and funding
9 authors.
Funding
Abstract
DLC1 encodes a RhoA GTPase-activating protein and tumor suppressor lost in cancer by genomic deletion or epigenetic silencing and loss of DLC1 gene transcription. We unexpectedly identified non-small cell lung cancer (NSCLC) cell lines and tumor tissue that expressed DLC1 mRNA yet lacked DLC1 protein expression. We determined that DLC1 was ubiquitinated and degraded by cullin 4A-RING ubiquitin ligase (CRL4A) complex interaction with DDB1 and the FBXW5 substrate receptor. siRNA-mediated suppression of cullin 4A, DDB1, or FBXW5 expression restored DLC1 protein expression in NSCLC cell lines. FBXW5 suppression-induced DLC1 reexpression was associated with a reduction in the levels of activated RhoA-GTP and in RhoA effector signaling. Finally, FBXW5 suppression caused a DLC1-dependent decrease in NSCLC anchorage-dependent and -independent proliferation. In summary, we identify a posttranslational mechanism for loss of DLC1 and a linkage between CRL4A-FBXW5-associated oncogenesis and regulation of RhoA signaling.
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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.