PXD025508

PXD025508 is an original dataset announced via ProteomeXchange.

Title	Oncogenic PKA signaling stabilizes MYC oncoproteins via an aurora kinase A-dependent mechanism
Description	Genetic alterations that activate protein kinase A (PKA) signaling are found across many tumor types, but their downstream oncogenic mechanisms are poorly understood. We used global phosphoproteomics and kinome activity profiling to map the conserved signaling outputs driven by diverse genetic changes that activate PKA in cancer. We define two consensus networks of effectors downstream of PKA in cancer models including melanoma and fibrolamellar carcinoma [FLC]. One is centered on RAS/MAPK components and a second involves Aurora Kinase A (AURKA). We find that AURKA stabilizes c-MYC and n-MYC protein levels and expression programs in PKA-dependent tumor models, in part via a positive feedback loop mediated by the oncogenic kinase PIM2. This process can be suppressed by conformation-disrupting AURKA inhibitors such as CD-532. Our findings elucidate two independent mechanisms of PKA-driven tumor cell growth and designate drug targets for study in FLC and other PKA-dependent malignancies.
HostingRepository	PRIDE
AnnounceDate	2023-02-09
AnnouncementXML	Submission_2023-02-09_06:17:28.481.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	JohnGordan
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2021-04-20 23:12:46	ID requested
⏵ 1	2023-02-09 06:17:28	announced

Dataset with its publication pending

submitter keyword: AURKA, fibrolamellar carcinoma, PIM2,PKA, MYC, liver cancer

John DozierGordan
contact affiliation	Department of Medicine (GI Oncology), UCSF, United States
contact email	john.gordan@ucsf.edu
lab head
JohnGordan
contact affiliation	University of California, San Francisco
contact email	john.gordan@ucsf.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD025508
     1. Label: PRIDE project
     2. Name: Oncogenic PKA signaling stabilizes MYC oncoproteins via an aurora kinase A-dependent mechanism