PXD005849

PXD005849 is an original dataset announced via ProteomeXchange.

Title	pSILAC mass spectrometry reveals ZFP91 as novel IMiD dependent substrate of the CRL4CRBN ligase - PART 1
Description	Thalidomide and its derivatives lenalidomide and pomalidomide (IMiDs) are effective treatments of hematologic malignancies. It was shown that IMiDs impart gain of function properties to the CUL4-RBX1-DDB1-CRBN (CRL4CRBN) ubiquitin ligase that enable binding, ubiquitination and degradation of key therapeutic targets such as IKFZ1, IKZF3 and CSNK1A1. While these substrates have been implicated as efficacy targets in multiple myeloma (MM) and 5q deletion associated myelodysplastic syndrome (del(5q)-MDS), other targets likely exist. Using a pulse-chase SILAC mass spectrometry-based proteomics approach, here we demonstrate that lenalidomide induces the ubiquitination and degradation of ZFP91. We establish that ZFP91 is a bona fide IMiD dependent CRL4CRBN substrate and further show that ZFP91 harbors a zinc finger (ZnF) motif, related to the IKZF1/3 ZnF, critical for IMiD dependent CRBN binding. These findings demonstrate that single time point pulse-chase SILAC mass spectrometry-based proteomics (pSILAC-MS) is a sensitive approach for target identification of small molecules inducing selective protein degradation.
HostingRepository	PRIDE
AnnounceDate	2017-05-29
AnnouncementXML	Submission_2017-05-29_02:40:35.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Eric Fischer
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Velos; Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2017-02-04 06:14:07	ID requested
⏵ 1	2017-05-29 02:40:36	announced

An J, Ponthier CM, Sack R, Seebacher J, Stadler MB, Donovan KA, Fischer ES, ubiquitin ligase. Nat Commun, 8():15398(2017) [pubmed]

curator keyword: Biological, Biomedical

submitter keyword: Lenalidomide, imids, zfp91, crbn, cereblon

Eric Sebastian Fischer
contact affiliation	BCMP, Harvard Medical School, Boston, USA Cancer Biology, Dana-Farber Cancer Institute, Boston, USA
contact email	eric_fischer@dfci.harvard.edu
lab head
Eric Fischer
contact affiliation	Dana-Farber Cancer Institute
contact email	eric_fischer@dfci.harvard.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD005849
     1. Label: PRIDE project
     2. Name: pSILAC mass spectrometry reveals ZFP91 as novel IMiD dependent substrate of the CRL4CRBN ligase - PART 1