PXD037182

PXD037182 is an original dataset announced via ProteomeXchange.

Title	The E3 ligase TRIM25 impairs apoptotic cell death in colon carcinoma cells through hnRNPH1-triggered destabilization of caspase-7 mRNA
Description	Therapy resistance is still a major reason for treatment failure in colorectal cancer (CRC). Previously, we identified the E3 ubiquitin ligase TRIM25 as a novel suppressor of caspase-2 translation, thereby contributing to apoptosis resistance of CRC cells towards chemotherapeutic drugs. We herein report the executioner caspase-7 being a further target of TRIM25. Results from gain and loss-of-function approaches and actinomycin D experiments indicate that TRIM25 attenuates caspase-7 expression mainly through a decrease in mRNA stability. Data from RNA pull-down assays with immunoprecipitated TRIM25 truncations indicate a direct TRIM25 binding to caspase-7 mRNA which is mediated by the PRY/SPRY domain which is also known to be highly relevant for protein-protein interactions. By employing TRIM25 immunoprecipitation, we identified the heterogeneous nuclear ribonucleoprotein H1 (hnRNPH1) as a novel TRIM25 binding protein involved in the control of caspase-7 mRNA stability. Notably, the interaction of both proteins was highly sensitive to RNase A treatment and again depended on the PRY/SPRY domain, thus indicating an indirect interaction of both proteins which is achieved through a common RNA binding. Ubiquitin affinity chromatography showed that hnRNPH1 and TRIM25 are targets of ubiquitin modification. Functionally, the ectopic expression of caspase-7 in CRC cells caused an increase in poly ADP-ribose polymerase (PARP) cleavage concomitant with a significant increase in apoptosis. Collectively, the negative regulation of caspase-7 by TRIM25 via hnRNPH1 implies a novel survival mechanism underlying chemotherapeutic drug resistance of CRC cells. Targeting of TRIM25 could therefore offer a promising strategy for reducing therapy resistance in CRC patients.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:58:51.060.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Christian Münch
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-10-05 00:49:21	ID requested
1	2023-01-05 03:52:01	announced
⏵ 2	2023-11-14 08:58:51	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: TRIM25, colon carcinoma cells, caspase-7, hnRNPH1, RNA binding proteins,Apoptosis

Christian Münch
contact affiliation	Institute of Biochemistry II, Faculty of Medicine, Goethe University, Frankfurt am Main, Germany Frankfurt Cancer Institute, Frankfurt am Main, Germany Cardio-Pulmonary Institute, Frankfurt am Main, Germany
contact email	bozkurt@med.uni-frankfurt.de
lab head
Christian Münch
contact affiliation	Goethe University Frankfurt
contact email	ch.muench@em.uni-frankfurt.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD037182
     1. Label: PRIDE project
     2. Name: The E3 ligase TRIM25 impairs apoptotic cell death in colon carcinoma cells through hnRNPH1-triggered destabilization of caspase-7 mRNA