PXD032835

PXD032835 is an original dataset announced via ProteomeXchange.

Title	Proteome integral solubility alteration high-throughput proteomics assay identifies Collectin-12 as a non-apoptotic microglial caspase-3 substrate.
Description	Caspases are a family of proteins mostly known for their role in the activation of the apoptotic pathway leading to cell death. In the last decade, caspases have been found to fulfil other tasks regulating the cell phenotype independently to cell death. Microglia are the immune cells of the brain responsible for the maintenance of physiological brain functions but can also be involved in disease progression when overactivated. We have previously described non 30 apoptotic roles of caspase-3 (CASP3) in the regulation of the inflammatory phenotype of microglial cells or pro-tumoral activation in the context of brain tumors. CASP3 can regulate protein functions by cleavage of their target and therefore could have multiple substrates. So far, identification of CASP3 substrates has been performed mostly in apoptotic conditions where CASP3 activity is highly upregulated and these approaches do not have the capacity to uncover CASP3 substrates at the physiological level. In our study, we aim at discovering high affinity substrates of CASP3 involved in the normal regulation of the cell. We used an unconventional approach by chemically reducing the basal level activity of CASP3 (by DEVD 38 fmk treatment) coupled to a Mass Spectrometry screen (PISA) to identify stabilized, and consequently, non-cleaved proteins in microglia cells. PISA identified several significantly stabilized proteins after DEVD-fmk treatment, including a few already known CASP3substrates which validated our approach. Among them, we focused on the Collectin12 (COLEC12 or CL-P1) transmembrane receptor and uncovered a potential role for CASP3 cleavage of COLEC12 in the regulation of the phagocytic capacity of microglial cells. Taken together, these findings suggest a new way to uncover non-apoptotic high-affinity substrates of CASP3 important for the modulation of microglia cell physiology.
HostingRepository	PRIDE
AnnounceDate	2023-05-10
AnnouncementXML	Submission_2023-05-10_15:05:02.563.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	MassimilianoGaetani
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-03-26 18:30:23	ID requested
⏵ 1	2023-05-10 15:05:04	announced

Grabert K, Engskog-Vlachos P, Š, kand, í, k M, Vazquez-Cabrera G, Murgoci AN, Keane L, Gaetani M, Joseph B, Cheray M, Proteome integral solubility alteration high-throughput proteomics assay identifies Collectin-12 as a non-apoptotic microglial caspase-3 substrate. Cell Death Dis, 14(3):192(2023) [pubmed]

submitter keyword: caspase-3, Solubility,PISA, non-apoptotic, Sustrates, COLEC12, Proteomics, Microglia

MassimilianoGaetani
contact affiliation	Chemical Proteomics, Division of Physiological Chemistry I, Dept. of Medical Biochemistry and Biophysics, Karolinska Institute, 17177 Stockholm, Sweden.
contact email	massimiliano.gaetani@ki.se
lab head
MassimilianoGaetani
contact affiliation	Karolinska Institutet
contact email	massimiliano.gaetani@ki.se
dataset submitter

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/2023/05/PXD032835

PRIDE project URI

• PRIDE
  1. PXD032835
     1. Label: PRIDE project
     2. Name: Proteome integral solubility alteration high-throughput proteomics assay identifies Collectin-12 as a non-apoptotic microglial caspase-3 substrate.