The loss of the polybromo-1 (PBRM1) subunit in a class of SWI/SNF chromatin remodelling complexes in clear cell renal cell carcinoma redirects the deficient complexes to aberrant enhancer regions. The catalytic subunit SMARCA4 of the PBRM1-deficient complexes recruits the nuclear factor-κB transcription factor to drive pro-tumorigenic programs.
This is a preview of subscription content, access via your institution
Access options
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$29.99 / 30 days
cancel any time
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
References
Nargund, A. M. et al. The SWI/SNF Protein PBRM1 Restrains VHL-Loss-Driven Clear Cell Renal Cell Carcinoma. Cell Rep. 18, 2893–2906 (2017). This paper first reports initiation of clear cell RCC tumours from loss of Vhl and Pbrm1 in mouse kidney.
Yao, X. et al. VHL deficiency drives enhancer activation of oncogenes in clear cell renal cell carcinoma. Cancer Discov. 7, 1284–1305 (2017). This paper shows that the epigenomic effect of VHL loss involves activation of enhancers of proto-oncogenes.
Xiao, L. et al. Targeting SWI/SNF ATPases in enhancer-addicted prostate cancer. Nature 601, 434–439 (2022). This paper shows that degradation of SWI/SNF ATPases dislodges multiple transcription factors from the chromatin.
Juvekar, A. et al. Bortezomib induces nuclear translocation of IκBα resulting in gene-specific suppression of NF-κB–dependent transcription and induction of apoptosis in CTCL. Mol. Cancer Res. 9, 183–194 (2011). This paper shows that bortezomib induces nuclear translocation and accumulation of IκBα, which associates with NF-κB and inhibits its DNA binding activity.
Teh, B. T. et al. Familial non-VHL non-papillary clear-cell renal cancer. Lancet 349, 848–849 (1997). This paper describes the involvement of other genes besides VHL in familial clear cell RCC.
Varela, I. et al. Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma. Nature 469, 539–542 (2011). This paper describes the high prevalence of PBRM1 mutations in clear cell RCC.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
This is a summary of: Yao, X. et al. PBRM1-deficient PBAF complexes target aberrant genomic loci to activate the NF-κB pathway in clear cell renal cell carcinoma. Nat. Cell Biol. https://doi.org/10.1038/s41556-023-01122-y (2023).
Rights and permissions
About this article
Cite this article
PBRM1 loss redirects chromatin remodelling complex to recruit oncogenic factors. Nat Cell Biol 25, 808–809 (2023). https://doi.org/10.1038/s41556-023-01148-2
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41556-023-01148-2
