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PXD041870

PXD041870 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitlePARP7-mediated ADP-ribosylation stabilizes FRA1 and restrains IRF3/IRF1-dependent apoptosis and immune signaling and in cancer cells
DescriptionPARP7 inhibitors suppress tumor growth in a cell autonomous manner and by activating the immune system through restoring immune signaling. Nevertheless, the targets of PARP7-mediated ADP-ribosylation that regulate innate immune signaling and cancer cell survival remain elusive. Here, we identified PARP7 as a nuclear and cysteine-specific mono-ADP-ribosyltransferase that modified proteins critical for regulating transcription, such as the AP-1 transcription factor FRA1. Loss of FRA1 ADP-ribosylation via PARP7 inhibition by RBN-2397 or mutation of the ADP-ribosylation site C97 increased FRA1 degradation by PSMC3 and the proteasome. We found that the reduction in FRA1 protein levels promoted IRF3 and IRF1-dependent innate immune signaling and CASP8-mediated apoptosis. Furthermore, we demonstrated that high PARP7 expression are critical for inducing apoptosis in FRA1-positive cancer cells using the PARP7 inhibitor. Collectively, our findings highlight the connected roles of PARP7 and FRA1 and emphasize the clinical potential of PARP7 inhibitors for FRA1-driven cancers.
HostingRepositoryPRIDE
AnnounceDate2024-01-26
AnnouncementXMLSubmission_2024-01-26_09:25:41.438.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterDeena Leslie Pedrioli
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListadenosine diphosphoribosyl (ADP-ribosyl) modified residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-04-28 02:17:29ID requested
12024-01-26 09:25:42announced
Publication List
10.1073/pnas.2309047120;
Manetsch P, B, ö, hi F, Nowak K, Leslie Pedrioli DM, Hottiger MO, PARP7-mediated ADP-ribosylation of FRA1 promotes cancer cell growth by repressing IRF1- and IRF3-dependent apoptosis. Proc Natl Acad Sci U S A, 120(49):e2309047120(2023) [pubmed]
Keyword List
submitter keyword: ADP-ribosylation, lung cancer,PARP7, FRA1
Contact List
Michael Hottiger
contact affiliationDepartment of Molecular Mechanisms of Disease University of Zurich Winterthurerstr. 190 8057 Zurich, Switzerland
contact emailmichael.hottiger@dmmd.uzh.ch
lab head
Deena Leslie Pedrioli
contact affiliationUniversity of Zürich
contact emaildeena.lesliepedrioli@dmmd.uzh.ch
dataset submitter
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