PXD035420-2

PXD035420 is an original dataset announced via ProteomeXchange.

Title	Substrate spectrum of PPM1D in the cellular response to DNA double strand breaks
Description	PPM1D (also known as WIP1) is a p53-regulated protein phosphatase that modulates the DNA damage response (DDR) by dephosphorylation of DDR proteins. Amplification of PPM1D gene or gain-of-function mutations are commonly found in cancer. Here, we employed chemical inhibition of PPM1D and quantitative mass spectrometry-based phosphoproteomics to identify the substrates of PPM1D upon induction of DNA double strand breaks (DSBs) by topoisomerase II poison etoposide. We identified 73 putative PPM1D substrates that are involved in DNA repair, regulation of transcription and RNA processing. One third of DSB-induced S/TQ phosphorylation sites are dephosphorylated by PPM1D, demonstrating that PPM1D only partially counteracts ATM/ATR/DNA-PK signaling. PPM1D-targeted phosphorylation sites are found in a specific amino acid sequence motif that is characterized by glutamic acid residues, high intrinsic disorder and poor evolutionary conservation. We identified a functionally uncharacterized protein Kanadaptin as ATM and PPM1D substrate upon DSB induction. We propose that PPM1D plays a role during the response to DSBs formation by regulating the phosphorylation of DNA- and RNA-binding proteins in intrinsically disordered regions.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:57:30.011.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Petra Beli
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480; Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2022-07-20 01:07:33	ID requested
1	2022-09-06 04:15:10	announced
⏵ 2	2023-11-14 08:57:30	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: Double strand breaks, ATM, WIP1, Kanadaptin,PPM1D, DNA damage

Petra Beli
contact affiliation	Institute of Molecular Biology, Ackermannweg 4, 55128 Mainz, Germany
contact email	p.beli@imb-mainz.de
lab head
Petra Beli
contact affiliation	Institute of Molecular Biology (IMB), Mainz, Germany
contact email	p.beli@imb-mainz.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD035420
     1. Label: PRIDE project
     2. Name: Substrate spectrum of PPM1D in the cellular response to DNA double strand breaks