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RUVBL1 and RUVBL2 are druggable MYC effector regulators in neuroblastoma cells

Siaw, Joachim Tetteh LU orcid ; Claeys, Arne ; Lai, Wei Yun ; Borenäs, Marcus ; Hilgert, Elien ; Bekaert, Sarah Lee ; Sanders, Ellen ; Kaya, Irem ; Van Dorpe, Jo and Speleman, Frank , et al. (2026) In iScience 29(4). p.1-11
Abstract

High-risk neuroblastoma is characterized by MYCN amplification and high MYCN or MYC gene expression. These patients have a poor prognosis and there is an urgent need for more effective drugs. While strategies to develop inhibitors that directly target the MYC proteins have remained largely unsuccessful, recent preclinical studies have identified ATR, a key protein of the DNA damage response, as a promising alternative therapeutic target. Here, we identified a strong RUVBL1 and RUVBL2 signature in transcriptomics data derived from different MYCN-driven mice tumors treated with ATR inhibitors. The RUVBL proteins form a complex with ATPase activity that has broad cellular functions and we demonstrate that pharmacological inhibition of this... (More)

High-risk neuroblastoma is characterized by MYCN amplification and high MYCN or MYC gene expression. These patients have a poor prognosis and there is an urgent need for more effective drugs. While strategies to develop inhibitors that directly target the MYC proteins have remained largely unsuccessful, recent preclinical studies have identified ATR, a key protein of the DNA damage response, as a promising alternative therapeutic target. Here, we identified a strong RUVBL1 and RUVBL2 signature in transcriptomics data derived from different MYCN-driven mice tumors treated with ATR inhibitors. The RUVBL proteins form a complex with ATPase activity that has broad cellular functions and we demonstrate that pharmacological inhibition of this protein complex results in a strong reduction of MYC(N) signaling, cell-cycle arrest, DNA damage, and apoptosis. We confirmed the association with MYCN and identified the RUVBL genes as independent prognostic biomarkers in human primary neuroblastoma data.

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publishing date
type
Contribution to journal
publication status
published
keywords
biological sciences, molecular biology, molecular neuroscience, neuroscience
in
iScience
volume
29
issue
4
article number
115236
pages
1 - 11
publisher
Elsevier
external identifiers
  • scopus:105033492471
  • pmid:41940329
ISSN
2589-0042
DOI
10.1016/j.isci.2026.115236
language
English
LU publication?
no
additional info
Publisher Copyright: © 2026 The Author(s)
id
df5487c6-b856-4985-8549-00489f007f7c
date added to LUP
2026-04-01 13:04:40
date last changed
2026-09-04 09:49:02
@article{df5487c6-b856-4985-8549-00489f007f7c,
  abstract     = {{<p>High-risk neuroblastoma is characterized by MYCN amplification and high MYCN or MYC gene expression. These patients have a poor prognosis and there is an urgent need for more effective drugs. While strategies to develop inhibitors that directly target the MYC proteins have remained largely unsuccessful, recent preclinical studies have identified ATR, a key protein of the DNA damage response, as a promising alternative therapeutic target. Here, we identified a strong RUVBL1 and RUVBL2 signature in transcriptomics data derived from different MYCN-driven mice tumors treated with ATR inhibitors. The RUVBL proteins form a complex with ATPase activity that has broad cellular functions and we demonstrate that pharmacological inhibition of this protein complex results in a strong reduction of MYC(N) signaling, cell-cycle arrest, DNA damage, and apoptosis. We confirmed the association with MYCN and identified the RUVBL genes as independent prognostic biomarkers in human primary neuroblastoma data.</p>}},
  author       = {{Siaw, Joachim Tetteh and Claeys, Arne and Lai, Wei Yun and Borenäs, Marcus and Hilgert, Elien and Bekaert, Sarah Lee and Sanders, Ellen and Kaya, Irem and Van Dorpe, Jo and Speleman, Frank and Durinck, Kaat and Hallberg, Bengt and Palmer, Ruth H. and Van den Eynden, Jimmy}},
  issn         = {{2589-0042}},
  keywords     = {{biological sciences; molecular biology; molecular neuroscience; neuroscience}},
  language     = {{eng}},
  month        = {{04}},
  number       = {{4}},
  pages        = {{1--11}},
  publisher    = {{Elsevier}},
  series       = {{iScience}},
  title        = {{RUVBL1 and RUVBL2 are druggable MYC effector regulators in neuroblastoma cells}},
  url          = {{http://dx.doi.org/10.1016/j.isci.2026.115236}},
  doi          = {{10.1016/j.isci.2026.115236}},
  volume       = {{29}},
  year         = {{2026}},
}