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 Kuster; Vanesa Fernández-Sáiz; Florian Bassermann

doi:10.1016/j.molcel.2020.12.046

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 journal › Article › peer-review

41 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 language	English
Pages (from-to)	1170-1186.e10
Journal	Molecular Cell
Volume	81
Issue number	6
DOIs	https://doi.org/10.1016/j.molcel.2020.12.046
State	Published - 18 Mar 2021

Keywords

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

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10.1016/j.molcel.2020.12.046

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Heider, M., Eichner, R., Stroh, J., Morath, V., Kuisl, A., Zecha, J., Lawatscheck, J., Baek, K., Garz, A. K., Rudelius, M., Deuschle, F. C., Keller, U., Lemeer, S., Verbeek, M., Götze, K. S., Skerra, A., Weber, W. A., Buchner, J., Schulman, B. A., ... Bassermann, F. (2021). The IMiD target CRBN determines HSP90 activity toward transmembrane proteins essential in multiple myeloma. Molecular Cell, 81(6), 1170-1186.e10. https://doi.org/10.1016/j.molcel.2020.12.046

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title = "The IMiD target CRBN determines HSP90 activity toward transmembrane proteins essential in multiple myeloma",

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.",

keywords = "CD98hc, CRBN, HSP90, IMiDs, LAT1, chaperones, multiple myeloma, protein quality control, radio-theranostics, ubiquitin",

author = "Michael Heider and Ruth Eichner and Jacob Stroh and Volker Morath and Anna Kuisl and Jana Zecha and Jannis Lawatscheck and Kheewoong Baek and Garz, {Anne Kathrin} and Martina Rudelius and Deuschle, {Friedrich Christian} and Ulrich Keller and Simone Lemeer and Mareike Verbeek and G{\"o}tze, {Katharina S.} and Arne Skerra and Weber, {Wolfgang A.} and Johannes Buchner and Schulman, {Brenda A.} and Bernhard Kuster and Vanesa Fern{\'a}ndez-S{\'a}iz and Florian Bassermann",

note = "Publisher Copyright: {\textcopyright} 2021 The Author(s)",

year = "2021",

month = mar,

day = "18",

doi = "10.1016/j.molcel.2020.12.046",

language = "English",

volume = "81",

pages = "1170--1186.e10",

journal = "Molecular Cell",

issn = "1097-2765",

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Heider, M, Eichner, R, Stroh, J, Morath, V, Kuisl, A, Zecha, J, Lawatscheck, J, Baek, K, Garz, AK, Rudelius, M, Deuschle, FC, Keller, U, Lemeer, S, Verbeek, M, Götze, KS , Skerra, A , Weber, WA , Buchner, J, Schulman, BA, Kuster, B, Fernández-Sáiz, V & Bassermann, F 2021, 'The IMiD target CRBN determines HSP90 activity toward transmembrane proteins essential in multiple myeloma', Molecular Cell, vol. 81, no. 6, pp. 1170-1186.e10. https://doi.org/10.1016/j.molcel.2020.12.046

TY - JOUR

T1 - The IMiD target CRBN determines HSP90 activity toward transmembrane proteins essential in multiple myeloma

AU - Heider, Michael

AU - Eichner, Ruth

AU - Stroh, Jacob

AU - Morath, Volker

AU - Kuisl, Anna

AU - Zecha, Jana

AU - Lawatscheck, Jannis

AU - Baek, Kheewoong

AU - Garz, Anne Kathrin

AU - Rudelius, Martina

AU - Deuschle, Friedrich Christian

AU - Keller, Ulrich

AU - Lemeer, Simone

AU - Verbeek, Mareike

AU - Götze, Katharina S.

AU - Skerra, Arne

AU - Weber, Wolfgang A.

AU - Buchner, Johannes

AU - Schulman, Brenda A.

AU - Kuster, Bernhard

AU - Fernández-Sáiz, Vanesa

AU - Bassermann, Florian

PY - 2021/3/18

Y1 - 2021/3/18

N2 - 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.

AB - 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.

KW - CD98hc

KW - CRBN

KW - HSP90

KW - IMiDs

KW - LAT1

KW - chaperones

KW - multiple myeloma

KW - protein quality control

KW - radio-theranostics

KW - ubiquitin

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U2 - 10.1016/j.molcel.2020.12.046

DO - 10.1016/j.molcel.2020.12.046

M3 - Article

C2 - 33571422

AN - SCOPUS:85101703457

SN - 1097-2765

VL - 81

SP - 1170-1186.e10

JO - Molecular Cell

JF - Molecular Cell

IS - 6

ER -

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

Abstract

Keywords

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