The IMiD target CRBN determines HSP90 activity toward transmembrane proteins essential in multiple myeloma

Michael Heider, Ruth Eichner, Jacob Stroh, Volker Morath, Anna Kuisl, Jana Zecha, Jannis Lawatscheck, Kheewoong Baek, Anne Kathrin Garz, Martina Rudelius, Friedrich Christian Deuschle, Ulrich Keller, Simone Lemeer, Mareike Verbeek, Katharina S. Götze, Arne Skerra, Wolfgang A. Weber, Johannes Buchner, Brenda A. Schulman, Bernhard KusterVanesa Fernández-Sáiz, Florian Bassermann

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

Heider et al. investigate the molecular function of immunomodulatory drugs (IMiDs) and describe their target, CRBN, as a transmembrane protein (TP)-specific co-chaperone of the HSP90-AHA1 axis. By disrupting CRBN-HSP90 interaction, IMiDs lead to destabilization of various TPs as CD98hc/LAT1, which serve as therapeutic targets in multiple myeloma.

Original languageEnglish
Pages (from-to)1170-1186.e10
JournalMolecular Cell
Volume81
Issue number6
DOIs
StatePublished - 18 Mar 2021

Keywords

  • CD98hc
  • CRBN
  • HSP90
  • IMiDs
  • LAT1
  • chaperones
  • multiple myeloma
  • protein quality control
  • radio-theranostics
  • ubiquitin

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