PXD018244

PXD018244 is an original dataset announced via ProteomeXchange.

Title	The IMiD receptor CRBN determines quality control of transmembrane proteins
Description	The complex architecture of transmembrane proteins requires quality control (QC) for folding and membrane positioning, a prerequisite for cellular homoeostasis and intercellular communication. However, it has remained unclear whether transmembrane proteins-specific QC hubs exist. Here we specify Cereblon (CRBN), the target of immunomodulatory drugs (IMiDs), as a co-chaperone that specifically determines chaperone activity of HSP90 towards transmembrane proteins by means of counteracting AHA1. This function is abrogated by IMiDs, which disrupt the interaction of CRBN with the closed conformation of HSP90. Cell surface proteomics identifies different transmembrane protein clients of the CRBN-AHA1-HSP90 nexus. Among these, we characterize the amino acid transporters LAT1 and CD98hc as determinants of IMiD activity in multiple myeloma (MM) both in vitro and in vivo. These data establish the CRBN-AHA1-HSP90 axis in the biogenesis of transmembrane proteins, link IMiD activity to tumor metabolism, and specify CD98 as an attractive diagnostic and therapeutic target in multiple myeloma.
HostingRepository	PRIDE
AnnounceDate	2021-02-18
AnnouncementXML	Submission_2021-02-17_23:01:01.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jana Zecha
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos; LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2020-03-29 23:25:11	ID requested
1	2021-02-17 21:53:21	announced
⏵ 2	2021-02-17 23:01:01	announced	2021-02-18: Updated project metadata.

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, G, ö, tze KS, Skerra A, Weber WA, Buchner J, Schulman BA, Kuster B, Fern, á, ndez-S, á, iz V, Bassermann F, The IMiD target CRBN determines HSP90 activity toward transmembrane proteins essential in multiple myeloma. Mol Cell, 81(6):1170-1186.e10(2021) [pubmed]

10.1016/J.MOLCEL.2020.12.046;

submitter keyword: human, Lumos, multiple myeloma, membrane proteins, IMiDs, chaperones

Bernhard Kuster
contact affiliation	Chair of protomeics and bioanalytics, Technical University of Munich, Freising, Germany
contact email	kuster@tum.de
lab head
Jana Zecha
contact affiliation	TUM
contact email	jana.zecha@tum.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD018244
     1. Label: PRIDE project
     2. Name: The IMiD receptor CRBN determines quality control of transmembrane proteins