ArticleCell death and differentiation2013
Induction of autophagy and senescence by knockdown of ROC1 E3 ubiquitin ligase to suppress the growth of liver cancer cells.
Article in Cell death and differentiation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 95 citations in OpenAlex.
- HSP90 shields ROC1/RBX1 from proteasomal degradation by CHIP E3 ubiquitin ligase to promote lung adenocarcinoma.Signal transduction and targeted therapy · 2026Article
- Neddylation: from regulatory mechanisms to clinical implications in cancer.Journal of advanced research · 2026Review
- Mesenchymal Stem Cell-Derived Exosomes Improve Aging-Related Changes in Liver Lipid Metabolism by Enhancing Autophagy.Aging cell · 2026Article
- Protein neddylation in lung tumorigenesis: Target validation and targeted therapy.Fundamental research · 2025Review
- Inhibiting neddylation: A new strategy for tumor therapy.Journal of pharmaceutical analysis · 2025Review
- Regulation of cellular senescence in tumor progression and therapeutic targeting: mechanisms and pathways.Molecular cancer · 2025Review
- Ubiquitination regulates autophagy in cancer: simple modifications, promising targets.Journal of translational medicine · 2024Review
- SCFAutophagy · 2024Article
- A Conversation with ChatGPT on Contentious Issues in Senescence and Cancer Research.Molecular pharmacology · 2024Article
- Protein neddylation and its role in health and diseases.Signal transduction and targeted therapy · 2024Review
- A common molecular and cellular pathway in developing Alzheimer and cancer.Biochemistry and biophysics reports · 2024Review
- Repression of YEATS2 induces cellular senescence in hepatocellular carcinoma and inhibits tumor growth.Cell cycle (Georgetown, Tex.) · 2024Article
- RING box protein-1(RBX1), a key component of SCF E3 ligase, induced multiple myeloma cell drug-resistance though suppressing p27.Cancer biology & therapy · 2023Article
- Targeting cullin neddylation for cancer and fibrotic diseases.Theranostics · 2023Review
- RNF4 silencing induces cell growth arrest and DNA damage by promoting nuclear targeting of p62 in hepatocellular carcinoma.Oncogene · 2022Article
- Genetic and Epigenetic Mechanisms Deregulate the CRL2Frontiers in genetics · 2022Article
- Long non-coding RNA DDX11-AS1 promotes esophageal carcinoma cell proliferation and migration through regulating the miR-514b-3p/RBX1 axis.Bioengineered · 2021Article
- Tumor-associated antigen Prame targets tumor suppressor p14/ARF for degradation as the receptor protein of CRL2Cell death and differentiation · 2021Article
- ROC1 promotes the malignant progression of bladder cancer by regulating p-IκBα/NF-κB signaling.Journal of experimental & clinical cancer research : CR · 2021Article
- Autophagy in liver diseases.World journal of hepatology · 2021Review
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Regulator of Cullins-1 (ROC1) or RING box protein-1 (RBX1) is an essential RING component of Cullin-RING ligase (CRL). Our previous studies showed that ROC1 is required for the growth of several cancer cell lines while ROC1 siRNA silencing inactivates CRL, leading to cell cycle arrest, cell senescence and/or apoptosis. However, it is completely unknown whether ROC1 knockdown triggers autophagic response by inactivating CRL. Moreover, the role of ROC1 in liver cancer remains elusive. In this study, we reported that ROC1 knockdown significantly inhibited the growth of liver cancer cells by sequentially and independently inducing autophagy and p21-dependent cell senescence. Mechanism analysis revealed that ROC1 silencing triggered autophagy by inhibition of mammalian target of rapamycin (mTOR) activity due to accumulation of mTOR-inhibitory protein Deptor, a substrate of CRL. Consistently, Deptor knockdown significantly blocked autophagy response upon ROC1 silencing. Biologically, autophagy response upon ROC1 silencing was a survival signal, and blockage of autophagy pathway sensitized cancer cells to apoptosis. Finally, we demonstrated that ROC1 was overexpressed in hepatocellular carcinomas, which is associated with poor prognosis of liver cancer patients. These findings suggest that ROC1 is an appealing drug target for liver cancer and provide a proof-of-concept evidence for a novel drug combination of ROC1 inhibitor and an autophagy inhibitor for effective treatment of liver cancer by enhancing apoptosis.
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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.