PXD024040

PXD024040 is an original dataset announced via ProteomeXchange.

Title	Investigating the target and off-target landscape of PLK1 small molecule inhibitor volasertib
Description	In this study we aimed to identify off-targets of polo-like kinase 1 (Plk1) small molecule inhibitor volasertib. Plk1 is an important cell cycle kinase and an attractive target for anticancer treatment. Volasertib is ATP-competitive small molecules that may also block the ATP-pocket of other proteins. Despite the fatal infections and negative survival in a phase III trial on volasertib in acute myeloid leukemia volasertib has been a promising treatment option in children with rhabdomyosarcoma. Therefore, there is a need to understand the nature of adverse effects that possibly originate from the off-target proteins. We used thermal proteome profiling (TPP) to identify proteins that have a change in the thermal stability after treatment with volasertib. The temperature of aggregation of several proteins involved in prostaglandin and phosphatidyl-inositol phosphate metabolism increased after treatment with volasertib. PIP4K2A and ZADH2 were stabilized both by treatment in living cells and cell lysate. Functional disruption of these proteins affects the immune response and fatty acid metabolism. In addition, volasertib was found to affect transcriptional coactivators, normal and alternative RNA splicing regulators and proteins involved in the intracellular transport regulation. Our data suggests that the identified proteins may contribute more to the understanding of anti-tumor effect of volasertib.
HostingRepository	PRIDE
AnnounceDate	2021-08-23
AnnouncementXML	Submission_2021-08-23_06:36:17.751.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Rozbeh Jafari
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-02-08 00:20:16	ID requested
1	2021-08-23 01:26:38	announced
⏵ 2	2021-08-23 06:36:18	announced	2021-08-23: Updated project metadata.

10.1096/FJ.202100457RR;

Goroshchuk O, Kolosenko I, Kunold E, Vidarsdottir L, Pirmoradian M, Azimi A, Jafari R, Palm-Apergi C, Thermal proteome profiling identifies PIP4K2A and ZADH2 as off-targets of Polo-like kinase 1 inhibitor volasertib. FASEB J, 35(7):e21741(2021) [pubmed]

submitter keyword: volasertib,LC-MS, leukemia, PLK1

Rozbeh Jafari
contact affiliation	Rozbeh Jafari, Karoliniska Institutet, Department of Oncology-Pathology (lab head)
contact email	rozbeh.jafari@ki.se
lab head
Rozbeh Jafari
contact affiliation	Karolinska Institutet
contact email	rozbeh.jafari@ki.se
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD024040
     1. Label: PRIDE project
     2. Name: Investigating the target and off-target landscape of PLK1 small molecule inhibitor volasertib