PXD048057-1

PXD048057 is an original dataset announced via ProteomeXchange.

Title	Kinome profiling of shControl and shFANCA THP1 cells treated with volasertib
Description	The Fanconi anemia (FA) pathway is a network of proteins critical to the preservation of genomic integrity and the prevention of cancer. FA proteins safeguard the genome by regulating the cell cycle and facilitating error-free repair of DNA damage. Bi-allelic mutation of genes encoding FA pathway proteins causes the cancer predisposition syndrome Fanconi anemia (FA), which is associated with a high incidence of acute myeloid leukemia (AML). Individuals with mono-allelic mutation of a subset FA genes do not develop FA but suffer increased lifetime risk of solid and hematological malignancies. Within the general population, approximately 14% of sporadic AMLs harbor damaging mutations within the FA pathway. Our previous work demonstrated that inhibition of the mitotic kinase PLK1 induced synthetic lethality in cells deficient for FANCA, the gene most frequently lost in FA. This finding corroborates work from others that have identified synthetic lethal interactions between PLK1 and additional FA genes (FANCG, BRCA1, and BRCA2). Together, these findings suggest that FA pathway mutations may serve as biomarkers for sensitivity to PLK1 inhibitors, which have demonstrated therapeutic efficacy in an undefined subset of AML patients. Here, THP1 AML cells were generated with shControl or shFANCA and treated with 10nM volasertib for 24 h prior to kinome profiling.
HostingRepository	PRIDE
AnnounceDate	2024-11-21
AnnouncementXML	Submission_2024-11-21_11:16:37.791.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Steven Angus
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-12-21 14:29:24	ID requested
⏵ 1	2024-11-21 11:16:38	announced

Dataset with its publication pending

submitter keyword: Polo-like kinase 1, kinase inhibitor, acute myeloid leukemia, Fanconi anemia

Elizabeth A. Sierra Potchanant
contact affiliation	Indiana University School of Medicine
contact email	esierra@iu.edu
lab head
Steven Angus
contact affiliation	Indiana University School of Medicine
contact email	sangus@iu.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD048057
     1. Label: PRIDE project
     2. Name: Kinome profiling of shControl and shFANCA THP1 cells treated with volasertib