Dataset Information

Global Phosphoproteomics of DYRK1A Inhibition in Glioblastoma Cells

ABSTRACT: Here we performed a detailed investigation to delineate the role of DYRK1A in glioblastoma, using both pharmacological and genetic tools combined with global phosphoproteomics. Our data show that DYRK1A inhibitors affect a much broader proportion of the phosphoproteome than DYRK1A knockdown. By overlaying these datasets we identify a pool of 61 putative novel DYRK1A targets, and validate CDC23 Ser588 as a bona-fide DYRK1A substrate. CDC23 is a ubiquitin ligase that degrades mitotic proteins, and DYRK1A inhibiton thereby leads to the accumulation of cyclin B and activation of CDK1.

INSTRUMENT(S): Q Exactive HF-X

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Astrocyte

DISEASE(S): Glioblastoma

SUBMITTER: Sean Humphrey

LAB HEAD: Sean Humphrey

PROVIDER: PXD020441 | Pride | 2021-04-22

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	20190625_HFX4_SeHu_Ari_DYRK1A_EasyPhos_Genetic_DYRK1A-siRNA-Dox48h_1.raw	Raw
	20190625_HFX4_SeHu_Ari_DYRK1A_EasyPhos_Genetic_DYRK1A-siRNA-Dox48h_2.raw	Raw
	20190625_HFX4_SeHu_Ari_DYRK1A_EasyPhos_Genetic_DYRK1A-siRNA-Dox48h_3.raw	Raw
	20190625_HFX4_SeHu_Ari_DYRK1A_EasyPhos_Genetic_DYRK1A-siRNA-Dox48h_4.raw	Raw
	20190625_HFX4_SeHu_Ari_DYRK1A_EasyPhos_Genetic_DYRK1A-siRNA-Dox72h_1.raw	Raw

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Publications

Global phosphoproteomics reveals DYRK1A regulates CDK1 activity in glioblastoma cells.

Recasens Ariadna A Humphrey Sean J SJ Ellis Michael M Hoque Monira M Abbassi Ramzi H RH Chen Brianna B Longworth Mitchell M Needham Elise J EJ James David E DE Johns Terrance G TG Day Bryan W BW Kassiou Michael M Yang Pengyi P Munoz Lenka L

Cell death discovery 20210416 1

Both tumour suppressive and oncogenic functions have been reported for dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A). Herein, we performed a detailed investigation to delineate the role of DYRK1A in glioblastoma. Our phosphoproteomic and mechanistic studies show that DYRK1A induces degradation of cyclin B by phosphorylating CDC23, which is necessary for the function of the anaphase-promoting complex, a ubiquitin ligase that degrades mitotic proteins. DYRK1A inhibition le ...[more]

PMID: 33863878

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