PXD023835-1

PXD023835 is an original dataset announced via ProteomeXchange.

Title	The regulatory landscape of the human HPF1- and ARH3-dependent ADP-ribosylome
Description	Despite the involvement of Poly(ADP-ribose) polymerase-1 (PARP1) in many important biological pathways, the target residues of PARP1-mediated ADP-ribosylation remain ambiguous. To explicate the ADP-ribosylation regulome, we analyzed human cells depleted for key regulators of PARP1 activity, histone PARylation factor 1 (HPF1) and ADP-ribosylhydrolase 3 (ARH3). Using quantitative proteomics, we quantified 1,596 ADPr sites, displaying a thousand-fold regulation across investigated knockout cells. We find that HPF1 and ARH3 inversely and homogenously regulate the serine ADP-ribosylome on a proteome-wide scale with consistent adherence to lysine-serine (KS)-motifs suggesting targeting is independent of HPF1 and ARH3. Our data reveal that ADPr globally exists as mono-ADP-ribosylation, and we detail a remarkable degree of histone co-modification with ADPr and other post-translational modifications. Strikingly, no HPF1-dependent target residue switch from serine to glutamate/aspartate was detectable in cells, which challenges current dogma related to PARP1 target residues. Collectively, we elucidate hitherto unappreciated processes related to cellular PARP1 activity.
HostingRepository	PRIDE
AnnounceDate	2021-10-07
AnnouncementXML	Submission_2021-10-07_07:15:41.979.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ivo Hendriks
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	adenosine diphosphoribosyl (ADP-ribosyl) modified residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-01-26 06:17:55	ID requested
⏵ 1	2021-10-07 07:15:42	announced
2	2021-10-11 04:11:14	announced	2021-10-11: Updated project metadata.
3	2021-10-11 04:13:26	announced	2021-10-11: Updated project metadata. 2021-10-11: Updated publication reference for PubMed record(s): 34625544.
4	2022-02-14 03:27:57	announced	2022-02-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: ADP-ribosylation, ADPr, PARP1, PAR, MAR, HPF1, ARH3, PARG, Af1521

Michael Lund Nielsen
contact affiliation	Proteomics program, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark
contact email	michael.lund.nielsen@cpr.ku.dk
lab head
Ivo Hendriks
contact affiliation	Novo Nordisk Foundation Center for Protein Research, University of Copenhagen
contact email	ivo.a.hendriks@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD023835
     1. Label: PRIDE project
     2. Name: The regulatory landscape of the human HPF1- and ARH3-dependent ADP-ribosylome