https://github.com/broadinstitute/depmap_target_birc6
A repo with code for the BIRC6 analysis project
Science Score: 13.0%
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○CITATION.cff file
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✓codemeta.json file
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○.zenodo.json file
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○Scientific vocabulary similarity
Low similarity (3.8%) to scientific vocabulary
Repository
A repo with code for the BIRC6 analysis project
Basic Info
- Host: GitHub
- Owner: broadinstitute
- Language: HTML
- Default Branch: master
- Size: 120 MB
Statistics
- Stars: 4
- Watchers: 12
- Forks: 0
- Open Issues: 0
- Releases: 0
Metadata Files
README.md
A ubiquitination cascade regulating the integrated stress response and survival in carcinomas
Lisa D. Cervia 1,2, , Tsukasa Shibue 1, , Ashir A. Borah 1 , Benjamin Gaeta 1 , Linh He 1 , Lisa Leung 1 , Naomi Li 1,2 , Sydney Moyer 1,2 , Brian Shim 1,2 , Nancy Dumont 1 , Alfredo Gonzalez 1 , Nolan Bick 1 , Mariya Kazachkova 1 , Joshua M. Dempster 1 , John M. Krill-Burger 1 , Federica Piccioni 1 , Namrata D. Udeshi 1 , Meagan E. Olive 1 , Steven A. Carr 1 , David E. Root 1 , James M. McFarland 1 , Francisca Vazquez 1, , William C. Hahn 1,2,
Targeting of mutated oncogenes has led to the identification of new targeted therapies. However, druggable oncogene mutations do not occur in most cancers. Systematic identification of signaling pathways required for the fitness of cancer cells will facilitate the development of new cancer therapies. We used gene essentiality measurements in 1,086 cancer cell lines to identify selective co-essentiality modules and found that a ubiquitin ligase complex composed ofUBA6,BIRC6,KCMF1 andUBR4,which encode an E1, E2 and two heterodimeric E3 subunits, respectively, is required for the survival of a subset of epithelial tumors that exhibit a high degree of aneuploidy. Suppressing BIRC6 in cell lines that are dependent on this complex led to a substantial reduction in cell fitnessin vitroand potent tumor regression in vivo. Mechanistically, BIRC6 suppression resulted in selective activation of the integrated stress response (ISR) by stabilization and upregulation of the heme-regulated inhibitor (HRI), a direct ubiquitination target of the UBA6/BIRC6/KCMF1/UBR4 complex. These observations uncover a novel ubiquitination cascade that regulates ISR and highlight the potential of ISR activation as a new therapeutic strategy.
Authors Affiliations: 1 Broad Institute of MIT and Harvard, Cambridge, Massachusetts; 2 Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts. These authors contributed equally to this article. These senior authors contributed equally to this article.
Owner
- Name: Broad Institute
- Login: broadinstitute
- Kind: organization
- Location: Cambridge, MA
- Website: http://www.broadinstitute.org/
- Twitter: broadinstitute
- Repositories: 1,083
- Profile: https://github.com/broadinstitute
Broad Institute of MIT and Harvard
GitHub Events
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- Watch event: 1
Last Year
- Watch event: 1
Issues and Pull Requests
Last synced: about 1 year ago
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- Total pull requests: 0
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- Average comments per issue: 0
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Past Year
- Issues: 0
- Pull requests: 0
- Average time to close issues: N/A
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- Issue authors: 0
- Pull request authors: 0
- Average comments per issue: 0
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- Bot issues: 0
- Bot pull requests: 0