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Corrigendum Free access | 10.1172/JCI152424

Ubiquitin ligase RNF8 suppresses Notch signaling to regulate mammary development and tumorigenesis

Li Li, Kiran Kumar Naidu Guturi, Brandon Gautreau, Parasvi S. Patel, Amine Saad, Mayako Morii, Francesca Mateo, Luis Palomero, Haithem Barbour, Antonio Gomez, Deborah Ng, Max Kotlyar, Chiara Pastrello, Hartland W. Jackson, Rama Khokha, Igor Jurisica, El Bachir Affar, Brian Raught, Otto Sanchez, Moulay Alaoui-Jamali, Miguel A. Pujana, Anne Hakem, and Razq Hakem

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Published July 1, 2021 - More info

Published in Volume 131, Issue 13 on July 1, 2021
J Clin Invest. 2021;131(13):e152424. https://doi.org/10.1172/JCI152424.
© 2021 American Society for Clinical Investigation
Published July 1, 2021 - Version history
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Related article:

Ubiquitin ligase RNF8 suppresses Notch signaling to regulate mammary development and tumorigenesis
Li Li, … , Anne Hakem, Razq Hakem
Li Li, … , Anne Hakem, Razq Hakem
Research Article Cell biology Oncology

Ubiquitin ligase RNF8 suppresses Notch signaling to regulate mammary development and tumorigenesis

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Abstract

The E3 ubiquitin ligase RNF8 plays critical roles in maintaining genomic stability by promoting the repair of DNA double-strand breaks (DSBs) through ubiquitin signaling. Abnormal activation of Notch signaling and defective repair of DSBs promote breast cancer risk. Here, we found that low expression of the full-length RNF8 correlated with poor prognosis for breast cancer patients. Our data revealed that in addition to its role in the repair of DSBs, RNF8 regulated Notch1 signaling and cell-fate determination of mammary luminal progenitors. Mechanistically, RNF8 acted as a negative regulator of Notch signaling by ubiquitylating the active NOTCH1 protein (N1ICD), leading to its degradation. Consistent with abnormal activation of Notch signaling and impaired repair of DSBs in Rnf8-mutant mammary epithelial cells, we observed increased risk of mammary tumorigenesis in mouse models for RNF8 deficiency. Notably, deficiency of RNF8 sensitized breast cancer cells to combination of pharmacological inhibitors of Notch signaling and poly(ADP-ribose) polymerase (PARP), suggesting implications for treatment of breast cancer associated with impaired RNF8 expression or function.

Authors

Li Li, Kiran Kumar Naidu Guturi, Brandon Gautreau, Parasvi S. Patel, Amine Saad, Mayako Morii, Francesca Mateo, Luis Palomero, Haithem Barbour, Antonio Gomez, Deborah Ng, Max Kotlyar, Chiara Pastrello, Hartland W. Jackson, Rama Khokha, Igor Jurisica, El Bachir Affar, Brian Raught, Otto Sanchez, Moulay Alaoui-Jamali, Miguel A. Pujana, Anne Hakem, Razq Hakem

×

Original citation: J Clin Invest. 2018;128(10):4525–4542. https://doi.org/10.1172/JCI120401

Citation for this corrigendum: J Clin Invest. 2021;131(13):e152424. https://doi.org/10.1172/JCI152424

During the preparation of this manuscript, tumor-free survival data rather than mammary tumor–free survival data were inadvertently included in Figure 1A. The correct figure panel for mammary tumor–free survival is below.

The authors regret the error.

Footnotes

See the related article at Ubiquitin ligase RNF8 suppresses Notch signaling to regulate mammary development and tumorigenesis.

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