PXD041870 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | PARP7-mediated ADP-ribosylation stabilizes FRA1 and restrains IRF3/IRF1-dependent apoptosis and immune signaling and in cancer cells |
Description | PARP7 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. |
HostingRepository | PRIDE |
AnnounceDate | 2024-01-26 |
AnnouncementXML | Submission_2024-01-26_09:25:41.438.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Deena Leslie Pedrioli |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | adenosine diphosphoribosyl (ADP-ribosyl) modified residue |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2023-04-28 02:17:29 | ID requested | |
⏵ 1 | 2024-01-26 09:25:42 | announced | |
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 affiliation | Department of Molecular Mechanisms of Disease University of Zurich Winterthurerstr. 190 8057 Zurich, Switzerland |
contact email | michael.hottiger@dmmd.uzh.ch |
lab head | |
Deena Leslie Pedrioli |
contact affiliation | University of Zürich |
contact email | deena.lesliepedrioli@dmmd.uzh.ch |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/01/PXD041870 |
PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD041870
- Label: PRIDE project
- Name: PARP7-mediated ADP-ribosylation stabilizes FRA1 and restrains IRF3/IRF1-dependent apoptosis and immune signaling and in cancer cells