PXD009155

PXD009155 is an original dataset announced via ProteomeXchange.

Title	A Quantitative Chemical Proteomics Approach Using a Novel Two-Probe System Enables System-Wide Analysis of Protein Prenylation
Description	Proteins prenylation, the post-translational attachment of a farnesyl or geranylgeranyl isoprenoid to one or more C-terminal cysteine residues, is an important modulator of localization and function of proteins such as the Ras isoforms, and a widely studied therapeutic target in number of cancer and other diseases. Despite its clinical importance, tools to interrogate prenylation and to quantify changes in response to treatment or disease on a global scale are lacking. Herein we report the development of two novel isoprenoid analogues, YnF and YnGG, which when used in combination with quantitative proteomics technologies enables the global profiling of prenylated proteins in living cells. The workflow enabled validation of a 51 prenylated CXXX-motif proteins, including seven novel farnesylated substrates, and 29 Rab proteins. Furthermore, we present tools which enable the detection of prenylated peptides at native abundance. We developed a quantitative strategy to decipher changes in prenylation in response to several inhibitors, including the clinically relevant farnesyl transferase inhibitor Tipifarnib, enabling in-cell dose responses of individual inhibitors, as well as shedding light on the alternative prenylation dynamics caused by inhibition of one prenyl transferase. Finally, we show how our methodology can be employed to further our understanding of prenylation in disease models such as Choroideremia by quantifying the effect of prenylation on 30 Rab substrates in response to Rep-1 knock-out.
HostingRepository	PRIDE
AnnounceDate	2019-03-29
AnnouncementXML	Submission_2019-04-03_07:30:27.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Julia Morales Sanfrutos
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	farnesylated residue; geranylgeranylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2018-03-09 03:34:14	ID requested
1	2019-03-29 09:18:23	announced
⏵ 2	2019-04-03 07:30:29	announced	Updated publication reference for PubMed record(s): 30936521.

Storck EM, Morales-Sanfrutos J, Serwa RA, Panyain N, Lanyon-Hogg T, Tolmachova T, Ventimiglia LN, Martin-Serrano J, Seabra MC, Wojciak-Stothard B, Tate EW, Dual chemical probes enable quantitative system-wide analysis of protein prenylation and prenylation dynamics. Nat Chem, 11(6):552-561(2019) [pubmed]

curator keyword: Technical, Biomedical

submitter keyword: Human, prenylation, chemical proteomics

Eduard W. Tate
contact affiliation	Department of Chemistry, Imperial College London, Exhibition Road, London SW7 2AZ, UK
contact email	e.tate@imperial.ac.uk
lab head
Julia Morales Sanfrutos
contact affiliation	CRG
contact email	jmsanfrutos@yahoo.es
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD009155
     1. Label: PRIDE project
     2. Name: A Quantitative Chemical Proteomics Approach Using a Novel Two-Probe System Enables System-Wide Analysis of Protein Prenylation