ArticleBMC cancer2012
Effects of partner proteins on BCA2 RING ligase activity.
Article in BMC cancer, 2012. 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, 29 citations in OpenAlex.
- Integrated Bioinformatics and Experimental Validation of Post-Translational Modification-Related Biomarkers in Myocardial Ischemia-Reperfusion Injury.Journal of cardiovascular translational research · 2026Article
- RNF115 aggravates tumor progression through regulation of CDK10 degradation in thyroid carcinoma.Cell biology and toxicology · 2024Article
- A Novel Role for RNF126 in the Promotion of G2 Arrest via Interaction With 14-3-3σ.International journal of radiation oncology, biology, physics · 2022Article
- Multifaceted Roles of the E3 Ubiquitin Ligase RING Finger Protein 115 in Immunity and Diseases.Frontiers in immunology · 2022Review
- Ring finger protein 126: a potential biomarker for colorectal cancer.Histology and histopathology · 2021Article
- RNF115 plays dual roles in innate antiviral responses by catalyzing distinct ubiquitination of MAVS and MITA.Nature communications · 2020Article
- Deubiquitinase ubiquitin-specific protease 9X regulates the stability and function of E3 ubiquitin ligase ring finger protein 115 in breast cancer cells.Cancer science · 2019Article
- 14-3-3ζ inhibits heme oxygenase-1 (HO-1) degradation and promotes hepatocellular carcinoma proliferation: involvement of STAT3 signaling.Journal of experimental & clinical cancer research : CR · 2019Article
- BCA2/Rabring7 Interferes with HIV-1 Proviral Transcription by Enhancing the SUMOylation of IκBα.Journal of virology · 2017Article
- The Role of BCA2 in the Endocytic Trafficking of EGFR and Significance as a Prognostic Biomarker in Cancer.Journal of Cancer · 2016Article
- Loss of RAD-23 Protects Against Models of Motor Neuron Disease by Enhancing Mutant Protein Clearance.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- BCA2/Rabring7 targets HIV-1 Gag for lysosomal degradation in a tetherin-independent manner.PLoS pathogens · 2014Article
- Regulation of metformin response by breast cancer associated gene 2.Neoplasia (New York, N.Y.) · 2013Article
- Spliceosomal introns in the 5' untranslated region of plant BTL RING-H2 ubiquitin ligases are evolutionary conserved and required for gene expression.BMC plant biology · 2013Article
- RNF115/BCA2 E3 ubiquitin ligase promotes breast cancer cell proliferation through targeting p21Waf1/Cip1 for ubiquitin-mediated degradation.Neoplasia (New York, N.Y.) · 2013Article
- Solubility-based genetic screen identifies RING finger protein 126 as an E3 ligase for activation-induced cytidine deaminase.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Expansion and diversification of BTL ring-H2 ubiquitin ligases in angiosperms: putative Rabring7/BCA2 orthologs.PloS one · 2013Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundBCA2 is an E3 ligase linked with hormone responsive breast cancers. We have demonstrated previously that the RING E3 ligase BCA2 has autoubiquitination activity and is a very unstable protein. Previously, only Rab7, tetherin, ubiquitin and UBC9 were known to directly interact with BCA2.
methodsHere, additional BCA2 binding proteins were found using yeast two-hybrid and bacterial-II-hybrid screening techniques with Human breast and HeLa cDNA libraries. Co-expression of these proteins was analyzed through IHC of TMAs. Investigation of the molecular interactions and effects were examined through a series of in vivo and in vitro assays.
resultsTen unique BCA2 interacting proteins were identified, two of which were hHR23a and 14-3-3sigma. Both hHR23a and 14-3-3sigma are co-expressed with BCA2 in breast cancer cell lines and patient breast tumors (n = 105). hHR23a and BCA2 expression was significantly correlated (P = < 0.0001 and P = 0.0113) in both nucleus and cytoplasm. BCA2 expression showed a statistically significant correlation with tumor grade. High cytoplasmic hHR23a trended towards negative nodal status. Binding to BCA2 by hHR23a and 14-3-3sigma was confirmed in vitro using tagged partner proteins and BCA2. hHR23a and 14-3-3sigma effect the autoubiquitination and auto-degradation activity of BCA2. Ubiquitination of hHR23a-bound BCA2 was found to be dramatically lower than that of free BCA2, suggesting that hHR23a promotes the stabilization of BCA2 by inactivating its autoubiquitination activity, without degradation of hHR23a. On the other hand, phosphorylated BCA2 protein is stabilized by interaction with 14-3-3sigma both with and without proteasome inhibitor MG-132 suggesting that BCA2 is regulated by multiple degradation pathways.
conclusionsThe interaction between BCA2 and hHR23a in breast cancer cells stabilizes BCA2. High expression of BCA2 is correlated with grade in breast cancer, suggesting regulation of this E3 ligase is important to cancer progression.
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