PXD043261-3

PXD043261 is an original dataset announced via ProteomeXchange.

Title	Ancistrocladinium A induces cell death in drug-resistant myeloma cells via targeting transcription and RNA splicing machinery and ATF4-dependent apoptotic pathway: a promising candidate as a drug for multiple myeloma
Description	N,C-coupled naphthylisoquinoline alkaloids like the natural product ancistrocladinium A, was known for its strong antiprotozoal activity, but had never explored for its antitumor activity. We found the alkaloid to be a very efficient anti-myeloma agent in various cell lines, including proteasome inhibitor-resistant cell lines and patient's primary CD138+ myeloma cells either alone or in combination approaches with the compounds carfilzomib or panobinostat. To gain further insight, we used an MS-based approach with the biotinylated derivative of Ancistrocladinium A, leading to an enrichment of RNA splicing associated proteins. We validated alternative pre-mRNA splicing by analyzing RNA gene expression and splicing using the human Clariom D gene array after treatment of INA-6 cells with the alkaloid. Important pathways with altered RNA expression levels included RNA processing, transcription and splicing, and the ribonucleoprotein complex. Pathways with altered RNA splicing included PSMB5 target genes and, therefore, a driver of unfolded protein response (UPR) along with transcription-associated and cell cycle-associated genes. Furthermore, we confirmed the splicing-induced protein expression of activating tran-scription factor 4 (ATF4), a key regulator of UPR. Finally, histone 2A (H2A) phosphorylation and PARP-1 cleavage as an indicator of apoptosis indicator was also detected. Taken together, an-cistrocladinium A can be considered as a potent agent against PI-resistance in MM either alone or in combination with clinically approved drugs.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:12:41.553.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Daniela Bruennert
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2023-06-24 06:18:41	ID requested
1	2023-10-24 13:28:52	announced
2	2023-11-14 09:11:50	announced	2023-11-14: Updated project metadata.
⏵ 3	2024-10-22 06:12:42	announced	2024-10-22: Updated project metadata.

Br, ü, nnert D, Seupel R, Goyal P, Bach M, Schraud H, Kirner S, K, ö, ster E, Feineis D, Bargou RC, Schlosser A, Bringmann G, Chatterjee M, Ancistrocladinium A Induces Apoptosis in Proteasome Inhibitor-Resistant Multiple Myeloma Cells: A Promising Therapeutic Agent Candidate. Pharmaceuticals (Basel), 16(8):(2023) [pubmed]

10.3390/ph16081181;

submitter keyword: Ancistrocladinium A, carfilzomib, RNA splicing, panobinostat, nanoLC-MS/MS,Multiple Myeloma, proteasome inhibitor resistance

Manik Chatterjee
contact affiliation	University Hospital Wuerzburg Comprehensive Cancer Center Mainfranken Translational Oncology
contact email	Chatterjee_M@ukw.de
lab head
Daniela Bruennert
contact affiliation	Universitätsklinikum Würzburg
contact email	Bruennert_d@ukw.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD043261
     1. Label: PRIDE project
     2. Name: Ancistrocladinium A induces cell death in drug-resistant myeloma cells via targeting transcription and RNA splicing machinery and ATF4-dependent apoptotic pathway: a promising candidate as a drug for multiple myeloma