PXD011595

PXD011595 is an original dataset announced via ProteomeXchange.

Title	aPKC controls endothelial growth by modulating c-Myc via FoxO1 DNA binding ability
Description	Strict regulation of proliferation is vital for development, whereas unregulated cell proliferation is a fundamental characteristic of cancer. The polarity protein atypical protein kinase C lambda/iota (aPKC lambda) is associated with cell proliferation through unknown mechanisms. In endothelial cells, suppression of aPKC lambda impairs proliferation despite hyperactivated mitogenic signaling. Here we show that aPKC lambda phosphorylates the DNA binding domain of forkhead box O1 (FoxO1) transcription factor, a gatekeeper of endothelial growth. Although mitogenic signaling excludes FoxO1 from the nucleus, consequently increasing c-Myc abundance and proliferation, aPKC lambda controls c-Myc expression via FoxO1/miR-34c signaling without affecting its localization. We find this pathway is strongly activated in the malignant vascular sarcoma, angiosarcoma, and aPKC inhibition reduces c-Myc expression and proliferation of angiosarcoma cells. Moreover, FoxO1 phosphorylation at Ser218 and aPKC expression correlates with poor patient prognosis. Our findings may provide a new therapeutic strategy for treatment of malignant cancers, like angiosarcoma.
HostingRepository	PRIDE
AnnounceDate	2019-11-12
AnnouncementXML	Submission_2019-11-12_15:37:20.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Scientific Service Group Biomolecular Mass Spectrometry
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2018-11-06 23:55:13	ID requested
⏵ 1	2019-11-12 15:37:21	announced

Riddell M, Nakayama A, Hikita T, Mirzapourshafiyi F, Kawamura T, Pasha A, Li M, Masuzawa M, Looso M, Steinbacher T, Ebnet K, Potente M, Hirose T, Ohno S, Fleming I, Gattenl, ö, hner S, Aung PP, Phung T, Yamasaki O, Yanagi T, Umemura H, Nakayama M, aPKC controls endothelial growth by modulating c-Myc via FoxO1 DNA-binding ability. Nat Commun, 9(1):5357(2018) [pubmed]

curator keyword: Biological

submitter keyword: Human, Immuno Precipitation, aPK, c-Myc, FoxO1, Human

Masanori Nakayama
contact affiliation	Laboratory for Cell Polarity and Organogenesis Max Planck Institute for Heart and Lung Research D-61231, Bad Nauheim, Germany
contact email	masanori.nakayama@mpi-bn.mpg.de
lab head
Scientific Service Group Biomolecular Mass Spectrometry
contact affiliation	Max Planck Institute for Heart and Lung Research
contact email	proteomics@mpi-bn.mpg.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD011595
     1. Label: PRIDE project
     2. Name: aPKC controls endothelial growth by modulating c-Myc via FoxO1 DNA binding ability