PXD020870

PXD020870 is an original dataset announced via ProteomeXchange.

Title	Nuclear phosphatidylinositol (3,4,5) triphosphate interactome uncovers an enrichment in nucleolar proteins
Description	Polyphosphoinositides (PPIn) play essential functions as lipid signalling molecules and many of their functions have been elucidated in the cytoplasm. However, PPIns are also intranuclear where they contribute to chromatin remodelling, transcription and mRNA splicing. The PPIn, phosphatidylinositol 3,4,5-triphosphate (PtdIns(3,4,5)P3) has been mapped to the nucleus and nucleoli but its role remains unclear in this subcellular compartment. To gain further insights into the nuclear functions of PtdIns(3,4,5)P3, we applied a previously developed quantitative mass spectrometry-based approach to identify the targets of PtdIns(3,4,5)P3 from isolated nuclei. We identified 179 potential PtdIns(3,4,5)P3-interacting proteins and gene ontology analysis for the biological functions of this dataset revealed an enrichment in RNA processing/splicing, cytokinesis, protein folding and DNA repair. Interestingly, about half of these interactors were common to nucleolar protein datasets, some of which had dual functions in rRNA transcription and DNA repair, including Poly(ADP-Ribose) Polymerase 1 (PARP1),. PARP1 was found to interact directly with PPIns and to co-localise with PtdIns(3,4,5)P3 in the nucleolus. Focusing on another factor involved in RNA processing, heterogeneous nuclear ribonucleoprotein U (hnRNPU/SAF-A) was also identified and validated as a direct PPIn-interacting protein. Deletion of the polybasic motif in its DNA binding domain prevented PPIn interaction. In conclusion, the PtdIns(3,4,5)P3 interactome reported here identified several nucleolar proteins and splicing factors and further pointed to roles for this lipid in these processes.
HostingRepository	PRIDE
AnnounceDate	2021-06-28
AnnouncementXML	Submission_2021-06-27_23:41:15.473.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Evangelia Papachristou
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue; deamidated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2020-08-12 04:51:13	ID requested
⏵ 1	2021-06-27 23:41:15	announced

Dataset with its publication pending

submitter keyword: Nuclear phosphoinisitides, nucleolus, PtdIns (3,4,5)P3 interactome, Poly(ADP-Ribose) Polymerase 1 (PARP1), heterogeneous nuclear ribonucleoprotein U (hnRNPU/SAF-A)

Aurélia E. Lewis
contact affiliation	University of Bergen
contact email	Aurelia.Lewis@uib.no
lab head
Evangelia Papachristou
contact affiliation	Senior Scientific Assistant
contact email	Eva.Papachristou@cruk.cam.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD020870
     1. Label: PRIDE project
     2. Name: Nuclear phosphatidylinositol (3,4,5) triphosphate interactome uncovers an enrichment in nucleolar proteins