PXD007629

PXD007629 is an original dataset announced via ProteomeXchange.

Title	Characterisation of the biflavonoid hinokiflavone as a pre-mRNA splicing modulator that inhibits SENP
Description	We have identified the plant biflavonoid hinokiflavone as an inhibitor of splicing in vitro and modulator of alternative splicing in cells. Chemical synthesis confirms hinokiflavone is the active molecule. Hinokiflavone inhibits splicing in vitro by blocking spliceosome assembly, preventing formation of the B complex. Cells treated with hinokiflavone show altered subnuclear organization specifically of splicing factors required for A complex formation, which relocalize together with SUMO1 and SUMO2 into enlarged nuclear speckles containing polyadenylated RNA. Hinokiflavone increases protein SUMOylation levels, both in in vitro splicing reactions and in cells. Hinokiflavone also inhibited a purified, E. coli expressed SUMO protease, SENP1, in vitro, indicating the increase in SUMOylated proteins results primarily from inhibition of de-SUMOylation. Using a quantitative proteomics assay we identified many SUMO2 sites whose levels increased in cells following hinokiflavone treatment, with the major targets including 6 proteins that are components of the U2 snRNP and required for A complex formation.
HostingRepository	PRIDE
AnnounceDate	2017-09-07
AnnouncementXML	Submission_2017-09-12_02:05:48.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Andrea Pawellek
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	2-pyrrolidone-5-carboxylic acid (Glu); 2-pyrrolidone-5-carboxylic acid (Gln); ubiquitination signature dipeptidyl lysine; phosphorylated residue; iodoacetamide derivatized residue; deamidated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2017-09-01 06:34:46	ID requested
1	2017-09-07 06:48:35	announced
⏵ 2	2017-09-12 02:05:49	announced	Updated publication reference for PubMed record(s): 28884683.

Pawellek A, Ryder U, Tammsalu T, King LJ, Kreinin H, Ly T, Hay RT, Hartley RC, Lamond AI, Characterisation of the biflavonoid hinokiflavone as a pre-mRNA splicing modulator that inhibits SENP. Elife, 6():(2017) [pubmed]

curator keyword: Biological

submitter keyword: Human embryonic kidney (HEK) suspension cells, SUMO2

Angus Iain Lamond
contact affiliation	Gene expression and Regulation, School of Life Sciences, University of Dundee, UK
contact email	a.i.lamond@dundee.ac.uk
lab head
Andrea Pawellek
contact affiliation	University of Dundee
contact email	a.pawellek@dundee.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD007629
     1. Label: PRIDE project
     2. Name: Characterisation of the biflavonoid hinokiflavone as a pre-mRNA splicing modulator that inhibits SENP