PXD037854

PXD037854 is an original dataset announced via ProteomeXchange.

Title	A role for the Trim33 ubiquitin ligase in cellular response to replicative stress
Description	Deregulation of RNA polymerase II (RNAPII) by oncoproteins, such as transcription factor Myc, interferes with DNA replication and is a major source of DNA damage and genomic instability. Ubiquitination is a key pathway controlling RNAPII activity via modification of RNAPII subunits or associated regulatory proteins. We uncover a mechanism for genome maintenance by ubiquitin ligase Trim33 and transcription factor E2f4. We show that Trim33 promotes E2f4 protein turnover, restricting interactions of E2f4 with chromatin and with the Recql DNA helicase. Replicative stress blunts Trim33-dependent regulation, which stimulates E2f4 and Recql recruitment to chromatin and facilitates recovery of DNA replication. Deletion of Trim33 triggers chronic recruitment of Recql to chromatin and accelerates DNA replication under stress, accompanied by compromised DDR signaling and DNA repair. Depletion of Trim33 in Myc-overexpressing cells leads to accumulation of replication-associated DNA damage and delays Myc-driven tumorigenesis. We propose that the Trim33-E2f4-Recql axis provides a mechanism to control DNA replication at transcriptionally active chromatin to maintain genome integrity.
HostingRepository	PRIDE
AnnounceDate	2023-07-24
AnnouncementXML	Submission_2023-07-24_04:09:50.871.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mohamed AliJarboui
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; iodoacetic acid derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2022-10-31 09:15:26	ID requested
⏵ 1	2023-07-24 04:09:51	announced

Dataset with its publication pending

submitter keyword: AP. AP-MS. LC-MS. Ubiquitination. Trim33. E2f4. Stress Response

Mohamed AliJarboui
contact affiliation	Senior Scientist Project manager Core Facility for Medical Bioanalytics Proteomics Platform Tübingen (PxP) Institute for Ophthalmic Research Eberhard-Karls University of Tuebingen Elfriede-Aulhorn-Str. 7 D-72076 Tuebingen. Germany.
contact email	mohamed-ali.Jarboui@uni-tuebingen.de
lab head
Mohamed AliJarboui
contact affiliation	Medical Bioanalytics, University Clinic Tuebingen
contact email	mohamed-ali.jarboui@uni-tuebingen.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD037854
     1. Label: PRIDE project
     2. Name: A role for the Trim33 ubiquitin ligase in cellular response to replicative stress