PXD025195

PXD025195 is an original dataset announced via ProteomeXchange.

Title	An androgen signaling axis uses a writer and a reader of ADP-ribosylation to control protein complex assembly
Description	Androgen 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.
HostingRepository	PRIDE
AnnounceDate	2021-04-23
AnnouncementXML	Submission_2021-05-28_04:31:48.256.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	JJ Park
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monomethylated residue; adenosine diphosphoribosyl (ADP-ribosyl) modified residue; phosphorylated residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2021-04-06 04:02:04	ID requested
1	2021-04-22 23:30:34	announced
⏵ 2	2021-05-28 04:31:49	announced	2021-05-28: Updated publication reference for PubMed record(s): 33976187.

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]

submitter keyword: Androgen receptor, Human, LC-MS, mono-ADP ribosyltransferase

Bryce M. Paschal
contact affiliation	Center for Cell Signaling Department of Biochemistry & Molecular Genetics University of Virginia, Charlottesville, VA, USA
contact email	bmp2h@virginia.edu
lab head
JJ Park
contact affiliation	University of Virginia
contact email	jp2ht@virginia.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/04/PXD025195

PRIDE project URI

• PRIDE
  1. PXD025195
     1. Label: PRIDE project
     2. Name: An androgen signaling axis uses a writer and a reader of ADP-ribosylation to control protein complex assembly