Atypical plant homeodomain of UBR7 functions as an H2BK120Ub ligase and breast tumor suppressor
Open accessAbstract
The roles of Plant Homeodomain (PHD) fingers in catalysis of histone modifications are unknown. We demonstrated that the PHD finger of Ubiquitin Protein Ligase E3 Component N-Recognin7 (UBR7) harbors E3 ubiquitin ligase activity toward monoubiquitination of histone H2B at lysine120 (H2BK120Ub). Purified PHD finger or full-length UBR7 monoubiquitinated H2BK120 in vitro, and loss of UBR7 drastically reduced H2BK120Ub genome-wide binding sites in MCF10A cells. Low UBR7 expression was correlated with occurrence of triple-negative breast cancer and metastatic tumors. Consistently, UBR7 knockdown enhanced the invasiveness, induced epithelial-to-mesenchymal transition and promoted metastasis. Conversely, ectopic expression of UBR7 restored these cellular phenotypes and reduced tumor growth. Mechanistically, UBR7 loss reduced H2BK120Ub levels on cell adhesion genes, including CDH4, and upregulated the Wnt/β-Catenin signaling pathway. CDH4 overexpression could partially revert UBR7-dependent cellular phenotypes. Collectively, our results established UBR7 as a histone H2B monoubiquitin ligase that suppresses tumorigenesis and metastasis of triple-negative breast cancer.
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Manumycin polyketides act as molecular glues between UBR7 and P53
Isobe, Y., Okumura, M., McGregor, L. M., Brittain, S. M., Jones, M. D., Liang, X., White, R., Forrester, W., McKenna, J. M., Tallarico, J. A., et al. (2020) · Nature Chemical Biology · doi:10.1038/s41589-020-0557-2 · Cited by 124 · see citing works
- Authors
- Adhikary, S., Chakravarti, D., Terranova, C., Sengupta, I., Maitituoheti, M., Dasgupta, A., Srivastava, D. K., Ma, J., Raman, A. T., Tarco, E., Sahin, A. A., Bassett, R., Yang, F., Tapia, C., Roy, S., Rai, K., & Das, C.
- Affiliations
- Saha Institute of Nuclear Physics (IN)
- The University of Texas MD Anderson Cancer Center (US)
- Indian Institute of Chemical Biology (IN)
- Corresponding author
- Roy, Siddhartha
- Rai, Kunal
- Das, Chandrima
- ORCID
- Venue
- Nature Communications
- Published
- 2019-03-28
- Volume
- 10
- Issue
- 1
- Pages
- 1398-1398
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC6438984
- OpenAlex
- W2923057516
- Cited by
- 57
- References
- 65
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 10 · 2023: 4 · 2022: 9 · 2021: 13 · 2020: 4 · 2019: 4
- FWCI
- 2.48
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Cancer Prevention and Research Institute of Texas (RP170067, CA160578)
- University Grants Commission
- University of Texas MD Anderson Cancer Center (RP170067, CA160578)
- National Cancer Institute (R00CA160578, K99CA160578, CA160578, P30CA016672)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- plant homeodomain finger, E3 ubiquitin ligase, histone H2B, triple-negative breast cancer, tumor suppressor, metastasis, epithelial-mesenchymal transition, CDH4, Wnt/β-catenin signaling, cell adhesion genes, MCF10A cells
- MeSH terms
- PHD Zinc Fingers, Animals, Cell Adhesion, Female, Histones, Humans, Mice, Nude, Neoplasm Metastasis, Neoplasm Transplantation, Transplantation, Heterologous, Cadherins, Histone Code, Ubiquitin-Protein Ligases, Cell Line, Tumor, Mice, Ubiquitination, Epithelial-Mesenchymal Transition, Wnt Signaling Pathway, Carcinogenesis, Triple Negative Breast Neoplasms
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