PXD010783

PXD010783 is an original dataset announced via ProteomeXchange.

Title	C16-ceramide is a natural regulatory ligand of p53 in cellular stress response
Description	Ceramides are important participants of signal transduction, regulating fundamental cellular processes. Here we report the mechanism for activation of p53 tumor suppressor by C16-ceramide. C16-ceramide tightly binds within the p53 DNA binding domain (Kd ~ 60 nM), in close vicinity to the Box V motif. This interaction is highly selective towards the ceramide acyl chain length with its C10 atom being proximal to Ser240 and Ser241. Ceramide binding stabilizes p53 and disrupts its complex with E3 ligase MDM2 leading to the p53 accumulation, nuclear translocation and activation of the downstream targets. This is a novel physiological mechanism of p53 activation, which is fundamentally different from the canonical p53 regulation through protein-protein interactions or post-translational modifications. The discovered mechanism is triggered by serum or folate deprivation implicating it in the cellular response to nutrient/metabolic stress. Our study establishes C16-ceramide as the first natural small molecule activating p53 through the direct binding.
HostingRepository	PRIDE
AnnounceDate	2018-12-04
AnnouncementXML	Submission_2018-12-04_04:07:19.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Natalia Krupenko
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2018-08-15 03:39:54	ID requested
1	2018-10-16 08:15:23	announced
⏵ 2	2018-12-04 04:07:21	announced	Updated project metadata.

Fekry B, Jeffries KA, Esmaeilniakooshkghazi A, Szulc ZM, Knagge KJ, Kirchner DR, Horita DA, Krupenko SA, Krupenko NI, -ceramide is a natural regulatory ligand of p53 in cellular stress response. Nat Commun, 9(1):4149(2018) [pubmed]

curator keyword: Biological

submitter keyword: p52, ceramide, regulatory ligand

Natalia Krupenko
contact affiliation	UNC Chapel Hill Nutrition Department
contact email	natalia_krupenko@unc.edu
lab head
Natalia Krupenko
contact affiliation	University of North Carolina Chapel Hill
contact email	natalia_krupenko@unc.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/10/PXD010783

PRIDE project URI

• PRIDE
  1. PXD010783
     1. Label: PRIDE project
     2. Name: C16-ceramide is a natural regulatory ligand of p53 in cellular stress response