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PXD018811

PXD018811 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleAn androgen signaling axis uses a writer and a reader of ADP-ribosylation to control protein complex assembly
DescriptionAndrogen signaling through the androgen receptor (AR) regulates multiple pathways in both normal and prostate cancer cells. Androgen regulates diverse aspects of the AR life cycle, including its post-translational modification, but understanding how specific modifications influence AR activity has been mostly elusive. Here, we show that androgen regulates AR through a pathway mediated by the mono-ADP ribosyltransferase, Parp7. We show that Parp7 ADP-ribosylates AR on multiple cysteines, and that a subset of these sites mediates agonist-specific recruitment of the E3 ligase Dtx3L/Parp9. Tandem macrodomains in Parp9 selectively recognize ADP ribosylated AR, and Dtx3L/Parp9 affects expression of a subset of AR-regulated genes. Parp7, ADP-ribosylation of AR, and AR-Dtx3L/Parp9 complex assembly are inhibited by 60 Olaparib, a compound used clinically to inhibit poly-ADP-ribosyltransferases Parp1/2. Our study reveals the components of a new androgen signaling axis that uses a writer and reader of ADP-ribosylation to modulate AR activity.
HostingRepositoryPRIDE
AnnounceDate2021-05-28
AnnouncementXMLSubmission_2021-05-28_02:59:41.263.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterJJ Park
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListL-glutamyl-5-poly(ADP-ribose); phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentLTQ Orbitrap Velos; Q Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-04-26 16:56:39ID requested
12021-05-28 02:59:42announced
Publication List
Yang CS, Jividen K, Kamata T, Dworak N, Oostdyk L, Remlein B, Pourfarjam Y, Kim IK, Du KP, Abbas T, Sherman NE, Wotton D, Paschal BM, Androgen signaling uses a writer and a reader of ADP-ribosylation to regulate protein complex assembly. Nat Commun, 12(1):2705(2021) [pubmed]
Keyword List
submitter keyword: mono-ADP-ribosyltransferase, macrodomain, androgen receptor, Parp7, Tiparp, Parp9, Dtx3L, Olaparib
Contact List
Bryce M. Paschal
contact affiliationCenter for Cell Signaling Department of Biochemistry & Molecular Genetics University of Virginia, Charlottesville, VA, USA
contact emailpaschal@virginia.edu
lab head
JJ Park
contact affiliationUniversity of Virginia
contact emailjp2ht@virginia.edu
dataset submitter
Full Dataset Link List
Dataset FTP location
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