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A consensus binding motif for the PP4 protein phosphatase reveals its role as a regulator of cohesin release

ABSTRACT: Regulation of protein activities through phosphorylation is a fundamental regulatory mechanism in all organisms. Phosphoprotein phosphatase 4 (PP4) is a conserved and essential enzyme that dephosphorylates serine and threonine residues in substrates. Despite the importance of PP4 general principles of substrate selection are unknown hampering the study of signal regulation by this phosphatase. Here we identify and characterize a general PP4 consensus binding motif, the FxxP motif, that binds to the EVH1 domain of the PP4R3 subunit of the trimeric holoenzyme. We find that the FxxP motif is present in multiple PP4 interacting proteins and that PP4 binding to the FxxP motif can be negatively regulated by phosphorylation hereby providing a mechanism for feeding kinase information into the motif. We identify an uncharacterized FxxP motif in the cohesin release factor WAPL and show that direct binding between WAPL and PP4 is required for cohesin release. Collectively our work uncovers basic principles of PP4 specificity with broad implications for understanding phoshorylation-mediated signaling in cells.

INSTRUMENT(S): Q Exactive Plus

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Arminja Kettenbach

PROVIDER: MSV000083438 | MassIVE | Wed Feb 13 15:47:00 GMT 2019

SECONDARY ACCESSION(S): PXD012695

REPOSITORIES: MassIVE

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