PXD024802

PXD024802 is an original dataset announced via ProteomeXchange.

Title	BAG3 suppresses ciliogenesis by regulating levels of OFD1
Description	By regulating several hallmarks of cancer, BAG3 exerts oncogenic functions in a wide variety of malignant diseases including glioblastoma (GBM) and triple-negative breast cancer (TNBC). Here we performed global proteomic/phosphoproteomic analyses of Crispr/Cas9-mediated isogenic BAG3 knockouts of the two GBM lines U343 and U251 in comparison to parental controls. Depletion of BAG3 evoked major effects on proteins involved in ciliogenesis/ciliary function and the activity of the related kinases aurora-kinase A (AURKA) and cyclin-dependent kinase-1 (CDK1). Cilia formation was significantly enhanced in BAG3 KO cells, a finding that could be confirmed in BAG3-proficient vs -deficient BT-549 TNBC cells, thus identifying a completely novel function of BAG3 as a negative regulator of ciliogenesis. Furthermore, we demonstrate that enhanced ciliogenesis and reduced expression of SNAI1 and ZEB1, two key transcription factors regulating epithelial to mesenchymal transition (EMT) is correlated to decreased cell migration and invasion, both in the GBM and TNBC BAG3 knockout cells. Our data obtained in two different tumor entities identify suppression of EMT and ciliogenesis as putative synergizing mechanisms of BAG3-driven tumor aggressiveness in therapy-resistant cancers.
HostingRepository	PRIDE
AnnounceDate	2021-06-21
AnnouncementXML	Submission_2021-06-21_08:18:47.005.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Marina Hoffmann
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-03-17 11:15:15	ID requested
⏵ 1	2021-06-21 08:18:47	announced

Dataset with its publication pending

submitter keyword: glioblastoma cells, phosphoproteome, proteome, BAG3, ciliogenesis, OFD1

Ivan Dikic
contact affiliation	Molecular Signaling group, Institute of biochemistry 2, Goethe University - Medical Faculty, Frankfurt am Main, Germany
contact email	dikic@biochem2.uni-frankfurt.de
lab head
Marina Hoffmann
contact affiliation	institute of biochemistry 2 (IBC2)
contact email	hoffmann@med.uni-frankfurt.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD024802
     1. Label: PRIDE project
     2. Name: BAG3 suppresses ciliogenesis by regulating levels of OFD1