PXD032716

PXD032716 is an original dataset announced via ProteomeXchange.

Title	Cdk1-mediated threonine phosphorylation of Sam68 modulates its RNA binding, alternative splicing activity, and cellular functions
Description	Sam68 is a member of the STAR family of proteins that directly link signal transduction with post-transcriptional gene regulation. Sam68 controls the alternative splicing of many oncogenic proteins and its role is modulated by post-translational modifications, including serine/threonine phosphorylation, that differ at various stages of the cell cycle. However, the molecular basis and mechanisms of these modulations remain largely unknown. Here, we combined mass spectrometry, NMR spectroscopy, and cell biology techniques to provide a comprehensive post-translational modification (PTM) mapping of Sam68 at different stages of the cell cycle in HEK293 and HCT116 cells. We established that Sam68 is specifically phosphorylated at T33 and T317 by Cdk1, and demonstrated that these phosphorylation events reduce the binding of Sam68 to RNA, control its cellular localization, and reduce its alternative splicing activity, leading to a reduction in the induction of apoptosis and an increase in the proliferation of HCT116 cells.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:41:33.929.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD032716
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Andrew Bottrill
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monomethylated residue; phosphorylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Velos; Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2022-03-23 02:52:39	ID requested
1	2023-03-11 03:12:26	announced
⏵ 2	2023-11-14 08:41:34	announced	2023-11-14: Updated project metadata.

10.6019/PXD032716;

Malki I, Liepina I, Kogelnik N, Watmuff H, Robinson S, Lightfoot A, Gonchar O, Bottrill A, Fry AM, Dominguez C, Cdk1-mediated threonine phosphorylation of Sam68 modulates its RNA binding, alternative splicing activity and cellular functions. Nucleic Acids Res, 50(22):13045-13062(2022) [pubmed]

submitter keyword: Warwick_RTP

Sam68

KHDRBS1

Dr Cyril Dominguez
contact affiliation	The Leicester Institute of Structural and Chemical Biology, Department of Molecular and Cell Biology, University of Leicester, Leicester LE1 7RH, UK
contact email	cd180@leicester.ac.uk
lab head
Andrew Bottrill
contact affiliation	University of Warwick
contact email	a.r.bottrill@gmail.com
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/2023/03/PXD032716

PRIDE project URI

• PRIDE
  1. PXD032716
     1. Label: PRIDE project
     2. Name: Cdk1-mediated threonine phosphorylation of Sam68 modulates its RNA binding, alternative splicing activity, and cellular functions