Dataset Information

Cdk1-mediated threonine phosphorylation of Sam68 modulates its RNA binding, alternative splicing activity, and cellular functions

ABSTRACT: 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.

INSTRUMENT(S): LTQ Orbitrap Velos, Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Andrew Bottrill

LAB HEAD: Dr Cyril Dominguez

PROVIDER: PXD032716 | Pride | 2023-03-11

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	180702_001_UL02428-NK-02.raw	Raw
	180713_002_UL02435-NK-01.raw	Raw
	180713_002_UL02435-NK-02.raw	Raw
	2019 10_33_29 AM;File Size_ 418647294 [Byte] (F016219).mzid.gz	Mzid
	2019 10_33_29 AM;File Size_ 418647294 [Byte] (F016219).mzid_2019_10_33_29_AM_File_Size__418647294__Byte__(F016219).MGF	Mzid

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Publications

Cdk1-mediated threonine phosphorylation of Sam68 modulates its RNA binding, alternative splicing activity and cellular functions.

Malki Idir I Liepina Inara I Kogelnik Nora N Watmuff Hollie H Robinson Sue S Lightfoot Adam A Gonchar Oksana O Bottrill Andrew A Fry Andrew M AM Dominguez Cyril C

Nucleic acids research 20221201 22

Sam68, also known as KHDRBS1, 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 spectromet ...[more]

PMID: 36537190

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