MassIVE MSV000082226

Complete Public PXD009369

Aurora B opposes PP1 function in mitosis through phosphorylation of the conserved RVxF binding motif in PP1 regulatory proteins

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Description

Protein phosphatase 1 (PP1) is a highly conserved protein phosphatase that opposes the actions of a diverse set of Ser-Thr protein kinases by controlling the majority of serine-threonine (Ser-Thr) dephosphorylation reactions in eukaryotes. PP1 gains substrate specificity through binding to a large number (> 200) of regulatory proteins that control PP1 localization, activity, and interactions with substrates. PP1 recognizes the well-characterized RVxF binding motif that is present many of these regulatory proteins, thus generating a multitude of distinct PP1 holoenzymes. Here we show that a subset of the RVxF binding motifs, in which x is a phosphorylatable amino acid (RV[S/T]F), were phosphorylated specifically during mitosis and that this phosphorylation event abrogated the interaction of PP1 with the regulatory protein. We determined that this phosphorylation was primarily governed by the mitotic protein kinase Aurora B and that high phosphorylation site stoichiometry of these sites was crucial to maintain phosphorylation of PP1 substrates during mitosis. We generated an antibody that recognizes the phosphorylated form of the RV[S/T]F motif (RVp[S/T]F) and used it to identify known PP1 regulatory proteins (KNL1, CDCA2 and RIF1) as well as multiple proteins that could potentially act as PP1 binding partners (UBR5, ASPM, SEH1 and ELYS) governed by this mechanism. Taken together, the work presented here suggests a general regulatory mechanism by which the coordinated activities of Aurora B and PP1 may control mitotic progression. [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: RVxF ; Aurora B ; Protein phosphatase 1 ; PP1 ; mitosis ; phosphorylation ; protein kinases ; KNL1 ; CDCA2 ; RIF1 ; UBR5 ; ASPM ; SEH1 ; ELYS ; motif

Contact

Principal Investigators:
(in alphabetical order) 		Arminja Kettenbach, The Geisel School of Medicine at Dartmouth, United States
Submitting User: madamo

Publications

Nasa I, Rusin SF, Kettenbach AN, Moorhead GB.
Aurora B opposes PP1 function in mitosis by phosphorylating the conserved PP1-binding RVxF motif in PP1 regulatory proteins.
Sci Signal. Epub 2018 May 15.

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