ArticleInternational journal of oncology2009
A novel mechanism whereby BRCA1/1a/1b fine tunes the dynamic complex interplay between SUMO-dependent/independent activities of Ubc9 on E2-induced ERalpha activation/repression and degradation in breast cancer cells.
Article in International journal of oncology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
15 citing papers in PubMed, 22 citations in OpenAlex.
- SUMOylation Wrestles With the Occurrence and Development of Breast Cancer.Frontiers in oncology · 2021Review
- TheGenes · 2019Article
- A Provocative Molecular Link between Mammographic Density and BRCA1-loss associated TNBC.International journal of human genetics and genetic disorders · 2019Article
- A novel Ubc9 -dependent pathway regulates SIRT1- ER-α Axis and BRCA1-associated TNBC lung metastasis.Integrative molecular medicine · 2017Article
- BRCA1 Mutation Leads to Deregulated Ubc9 Levels which Triggers Proliferation and Migration of Patient-Derived High Grade Serous Ovarian Cancer and Triple Negative Breast Cancer Cells.International journal of chronic diseases & therapy · 2016Article
- Polymorphism of UBC9 gene encoding the SUMO-E2-conjugating enzyme and breast cancer risk.Pathology oncology research : POR · 2014Article
- Identification of a non-canonical nuclear localization signal (NLS) in BRCA1 that could mediate nuclear localization of splice variants lacking the classical NLS.Cellular & molecular biology letters · 2013Article
- Ubiquitin- and ubiquitin-like proteins-conjugating enzymes (E2s) in breast cancer.Molecular biology reports · 2013Article
- Triple Negative Breast Cancer - An Overview.Hereditary genetics : current research · 2013Article
- Article
- BRCA1 proteins regulate growth of ovarian cancer cells by tethering Ubc9.American journal of cancer research · 2012Article
- Ubc9 mediates nuclear localization and growth suppression of BRCA1 and BRCA1a proteins.Journal of cellular physiology · 2011Article
- Elevated global SUMOylation in Ubc9 transgenic mice protects their brains against focal cerebral ischemic damage.PloS one · 2011Article
- Role of the BCA2 ubiquitin E3 ligase in hormone responsive breast cancer.The open cancer journal · 2010Article
- A Novel Pathway that Links Caveolin-1 Down-Regulation to BRCA1 Dysfunction in Serous Epithelial Ovarian Cancer Cells.Enliven. Challenges in cancer detection and therapyArticle
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
BRCA1 dysfunction is associated with hormone-responsive cancers. We have identified a consensus SUMO modification site in the amino-terminal region of BRCA1/1a/1b proteins and the mutation in this potential SUMO acceptor site (K 109 to R) impaired their ability to bind and repress ligand-dependent ERalpha transcriptional activity in breast cancer cells. Furthermore, we have found SUMO E2-conjugating enzyme Ubc9 to bind BRCA1 proteins. We have mapped BRCA1 [within amino acids (aa) 1-182] as the minimum domain that is sufficient for in vitro binding to Ubc9 as well as for regulating ERalpha activity. BRCA1 Mutant #1 (K109 to R) was impaired in its ability to both bind, as well as modulate Ubc9 mediated SUMO-dependent/independent E2-induced ERalpha transcriptional activity in breast cancer cells. Similarly, BRCA1 cancer-predisposing mutation (61Cys-Gly) abrogated the ability to both bind Ubc9 as well as inhibit ERalpha activity suggesting physiological significance. Addition of BRCA1 but not Mutant #1 to E2-induced ERalpha in the presence of SUMO-1 and Ubc9 resulted in the degradation of ERalpha suggesting BRCA1 to be a putative SUMO-1 and Ubc9-dependent E3 ubiquitin ligase for ERalpha. This is the first report demonstrating the participation of Ubc9 in BRCA1 E3 ubiquitin ligase mediated degradation of ERalpha. These results suggest a novel function for BRCA1 in regulating the dynamic cycles of SUMO and ubiquitin modifications required for ERalpha turn over and deregulation of this molecular switch due to lack of BRCA1 results in ERalpha-negative/positive breast cancers. This study will help in designing novel BRCA1 function-based targeted treatment for breast cancers.
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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.