Nature Communications (2021-02-01)

Targeting NSD2-mediated SRC-3 liquid–liquid phase separation sensitizes bortezomib treatment in multiple myeloma

  • Jing Liu,
  • Ying Xie,
  • Jing Guo,
  • Xin Li,
  • Jingjing Wang,
  • Hongmei Jiang,
  • Ziyi Peng,
  • Jingya Wang,
  • Sheng Wang,
  • Qian Li,
  • Linquan Ye,
  • Yuping Zhong,
  • Qiguo Zhang,
  • Xiaozhi Liu,
  • David M. Lonard,
  • Jin Wang,
  • Bert W. O’Malley,
  • Zhiqiang Liu

DOI
https://doi.org/10.1038/s41467-021-21386-y
Journal volume & issue
Vol. 12, no. 1
pp. 1 – 14

Abstract

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The mechanisms behind acquired resistance to the proteasome inhibitor bortezomib in multiple myeloma remain to be elucidated. Here, the authors show that the histone methyltransferase NSD2 stabilized SRC-3 protein levels, promotes its phase separation and alters H3K36me2 at certain gene promoters resulting in a transcriptional profile that favors resistance of myeloma cells to bortezomib.