PXD021420

PXD021420 is an original dataset announced via ProteomeXchange.

Title	Phosphorylation of SMURF2 by ATM exerts a negative feedback control of DNA damage response
Description	Timely repair of DNA double-strand breaks (DSBs) is essential to maintaining genomic integrity and preventing illnesses induced by genetic abnormalities. We previously demonstrated that the E3 ubiquitin ligase Smad ubiquitin regulatory factor 2 (SMURF2) plays a critical tumor suppressing role via its interaction with ring finger protein 20 (RNF20) in shaping chromatin landscape and preserving genomic stability. Here, we show that upon the onset of the DNA-damage response, Smurf2 becomes phosphorylated at S384 by ataxia telangiectasia mutated (ATM) and this phosphorylation is required for its interaction with RNF20. We demonstrate that Smurf2 mutant with an S384A substitution has reduced capacity to ubiquitinate RNF20 while promoting Smad3 ubiquitination unabatedly. More importantly, mouse embryonic fibroblasts (MEFs) expressing the SMURF2 S384A mutant show a weakened ability to sustain the DSB response compared to those expressing wild type SMURF2 following etoposide treatment. These data indicate that SMURF2-mediated RNF20 ubiquitination and degradation controlled by ATM-induced phosphorylation at S384 constitutes a negative feedback loop that regulates DSB repair.
HostingRepository	PRIDE
AnnounceDate	2020-10-26
AnnouncementXML	Submission_2020-10-26_04:07:20.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD021420
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Liuya Tang
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; monohydroxylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2020-09-10 23:36:54	ID requested
⏵ 1	2020-10-26 04:07:21	announced

Tang LY, Thomas A, Zhou M, Zhang YE, Phosphorylation of SMURF2 by ATM exerts a negative feedback control of DNA damage response. J Biol Chem, 295(52):18485-18493(2020) [pubmed]

submitter keyword: SMURF2, ATM, phosphorylation, DNA damage response

Ying E. Zhang
contact affiliation	Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892
contact email	zhangyin@mail.nih.gov
lab head
Liuya Tang
contact affiliation	NIH
contact email	tangl2@mail.nih.gov
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD021420
     1. Label: PRIDE project
     2. Name: Phosphorylation of SMURF2 by ATM exerts a negative feedback control of DNA damage response