PXD001297

PXD001297 is an original dataset announced via ProteomeXchange.

Title	The Nuclear Proteome of a Vertebrate
Description	Despite the nucleus’ central role in multi-cellular biology, it is still poorly understood how the cell’s proteome is partitioned between the nucleus and cytoplasm. This is mostly due to the difficulty of separating the nuclear and cytoplasmic contents and the challenge to comprehensively measure relative protein abundance. Here, we quantify the nucleocytoplasmic distribution for more than 9000 proteins of the Xenopus laevis oocyte, with two different methods of quantitative proteomics. We find a trimodal distribution, with most proteins localizing exclusively to either the nucleus or the cytoplasm, and where a third subset is equidistributed. By measuring the physiological protein size in undiluted cell lysate we show that nearly all partitioned proteins behave according to a molecular weight larger than ~100kDa, while physiologically smaller proteins are typically equipartitioned. To investigate the role of nuclear export on segregation of nuclear and cytoplasmic contents, we followed nucleocytoplasmic protein localization upon inhibition of the nuclear export receptor Exportin 1 with Leptomycin B (LMB). After 24h of perturbation only a small subset of proteins relocated significantly towards the nucleus suggesting that protein assembly and passive retention, rather than active nuclear transport , are primarily responsible for the maintenance of nuclear composition. Among the proteins that respond to LMB we find a significant overrepresentation of kinases, suggesting an intriguing explanation for the efficacy of Exportin 1 inhibitors in the treatment of various cancers. Thus, we present the first resource for the quantitative nucleocytoplasmic partitioning of a proteome, measure its dynamics upon perturbation, shed new light on the mechanisms of subcellular protein localization, and suggest novel mechanisms of action for promising cancer therapeutics.
HostingRepository	PRIDE
AnnounceDate	2015-09-17
AnnouncementXML	Submission_2015-10-14_05:02:15.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Martin Wuehr
SpeciesList	scientific name: Xenopus laevis (African clawed frog); NCBI TaxID: 8355;
ModificationList	monohydroxylated residue; TMT6plex-126 reporter+balance reagent acylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2014-09-09 02:01:39	ID requested
1	2015-09-17 04:48:27	announced
⏵ 2	2015-10-14 05:02:16	announced	Updated publication reference for PubMed record(s): 26441354.

W, ü, hr M, G, ü, ttler T, Peshkin L, McAlister GC, Sonnett M, Ishihara K, Groen AC, Presler M, Erickson BK, Mitchison TJ, Kirschner MW, Gygi SP, The Nuclear Proteome of a Vertebrate. Curr Biol, 25(20):2663-71(2015) [pubmed]

curator keyword: Biological

submitter keyword: Nucleus, Xenopus, TMTC, MultiNotchMS3,

Steven Gygi
contact affiliation	Department of Cell Biology, Harvard Medical School, Boston, MA, USA
contact email	steven_gygi@hms.harvard.edu
lab head
Martin Wuehr
contact affiliation	Harvard Medical School
contact email	martin.wuehr@gmx.de
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/2015/09/PXD001297

PRIDE project URI

• PRIDE
  1. PXD001297
     1. Label: PRIDE project
     2. Name: The Nuclear Proteome of a Vertebrate