RNF126 promotes homologous recombination via regulation of E2F1-mediated BRCA1 expression

Y. Wang, O. Deng, Z. Feng, Z. Du, X. Xiong, J. Lai, X. Yang, M. Xu, H. Wang, D. Taylor, Chunhong Yan, C. Chen, A. Difeo, Z. Ma, J. Zhang

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

RNF126 is an E3 ubiquitin ligase. The deletion of RNF126 gene was observed in a wide range of human cancers and is correlated with improved disease-free and overall survival. These data highlight the clinical relevance of RNF126 in tumorigenesis and cancer therapy. However, the specific functions of RNF126 remain largely unknown. Homologous recombination (HR)-mediated DNA double-strand break repair is important for tumor suppression and cancer therapy resistance. Here, we demonstrate that RNF126 facilitates HR by promoting the expression of BRCA1, in a manner independent of its E3 ligase activity but depending on E2F1, a well-known transcription factor of BRCA1 promoter. In support of this result, RNF126 promotes transactivation of BRCA1 promoter by directly binding to E2F1. Most importantly, an RNF126 mutant lacking 11 amino acids that is responsible for the interaction with E2F1 has a dominant-negative effect on BRCA1 expression and HR by suppressing E2F1-mediated transactivation of BRCA1 promoter and blocking the enrichment of E2F1 on BRCA1 promoter. Lastly, RNF126 depletion leads to the increased sensitivity to ionizing radiation and poly (ADP-ribose) polymerase inhibition. Collectively, our results suggest a novel role of RNF126 in promoting HR-mediated repair through positive regulation on BRCA1 expression by direct interaction with E2F1. This study not only offers novel insights into our current understanding of the biological functions of RNF126 but also provides a potential therapeutic target for cancer treatment.

Original languageEnglish (US)
Pages (from-to)1363-1372
Number of pages10
JournalOncogene
Volume35
Issue number11
DOIs
StatePublished - Mar 17 2016

Fingerprint

Homologous Recombination
Ubiquitin-Protein Ligases
Neoplasms
Transcriptional Activation
Recombinational DNA Repair
Double-Stranded DNA Breaks
Poly(ADP-ribose) Polymerases
Gene Deletion
Ionizing Radiation
Disease-Free Survival
Carcinogenesis
Transcription Factors
Therapeutics
Amino Acids

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Wang, Y., Deng, O., Feng, Z., Du, Z., Xiong, X., Lai, J., ... Zhang, J. (2016). RNF126 promotes homologous recombination via regulation of E2F1-mediated BRCA1 expression. Oncogene, 35(11), 1363-1372. https://doi.org/10.1038/onc.2015.198

RNF126 promotes homologous recombination via regulation of E2F1-mediated BRCA1 expression. / Wang, Y.; Deng, O.; Feng, Z.; Du, Z.; Xiong, X.; Lai, J.; Yang, X.; Xu, M.; Wang, H.; Taylor, D.; Yan, Chunhong; Chen, C.; Difeo, A.; Ma, Z.; Zhang, J.

In: Oncogene, Vol. 35, No. 11, 17.03.2016, p. 1363-1372.

Research output: Contribution to journalArticle

Wang, Y, Deng, O, Feng, Z, Du, Z, Xiong, X, Lai, J, Yang, X, Xu, M, Wang, H, Taylor, D, Yan, C, Chen, C, Difeo, A, Ma, Z & Zhang, J 2016, 'RNF126 promotes homologous recombination via regulation of E2F1-mediated BRCA1 expression', Oncogene, vol. 35, no. 11, pp. 1363-1372. https://doi.org/10.1038/onc.2015.198
Wang, Y. ; Deng, O. ; Feng, Z. ; Du, Z. ; Xiong, X. ; Lai, J. ; Yang, X. ; Xu, M. ; Wang, H. ; Taylor, D. ; Yan, Chunhong ; Chen, C. ; Difeo, A. ; Ma, Z. ; Zhang, J. / RNF126 promotes homologous recombination via regulation of E2F1-mediated BRCA1 expression. In: Oncogene. 2016 ; Vol. 35, No. 11. pp. 1363-1372.
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AU - Wang, H.

AU - Taylor, D.

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