A Consensus Binding Motif for the PP4 Protein Phosphatase

Yumi Ueki; Thomas Kruse; Melanie Bianca Weisser; Gustav N Sundell; Marie Sofie Yoo Larsen; Blanca Lopez Mendez; Nicole P Jenkins; Dimitriya H Garvanska; Lauren Cressey; Gang Zhang; Norman Davey; Guillermo Montoya; Ylva Ivarsson; Arminja N Kettenbach; Jakob Nilsson

doi:10.1016/j.molcel.2019.08.029

A Consensus Binding Motif for the PP4 Protein Phosphatase

Bidragets oversatte titel: Et bindings motiv for PP4 fosfatasen: NA

Yumi Ueki, Thomas Kruse, Melanie Bianca Weisser, Gustav N Sundell, Marie Sofie Yoo Larsen, Blanca Lopez Mendez, Nicole P Jenkins, Dimitriya H Garvanska, Lauren Cressey, Gang Zhang, Norman Davey, Guillermo Montoya, Ylva Ivarsson, Arminja N Kettenbach, Jakob Nilsson

10 Citationer (Scopus)

Abstract

NA

Bidragets oversatte titel	Et bindings motiv for PP4 fosfatasen: NA
Originalsprog	Engelsk
Tidsskrift	Molecular Cell
ISSN	1097-2765
DOI	https://doi.org/10.1016/j.molcel.2019.08.029
Status	Udgivet - 19 dec. 2019

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10.1016/j.molcel.2019.08.029

http://www.cell.com/article/S1097276519306847/pdf

Citationsformater

@article{ff2b91a63f404b1c8682cfc3699b59e1,

title = "A Consensus Binding Motif for the PP4 Protein Phosphatase",

abstract = "Dynamic protein phosphorylation constitutes a fundamental regulatory mechanism in all organisms. Phosphoprotein phosphatase 4 (PP4) is a conserved and essential nuclear serine and threonine phosphatase. 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 thoroughly characterize a general PP4 consensus-binding motif, the FxxP motif. X-ray crystallography studies reveal that FxxP motifs bind to a conserved pocket in the PP4 regulatory subunit PPP4R3. Systems-wide in silico searches integrated with proteomic analysis of PP4 interacting proteins allow us to identify numerous FxxP motifs in proteins controlling a range of fundamental cellular processes. We identify an FxxP motif in the cohesin release factor WAPL and show that this regulates WAPL phosphorylation status and is required for efficient cohesin release. Collectively our work uncovers basic principles of PP4 specificity with broad implications for understanding phosphorylation-mediated signaling in cells.",

author = "Yumi Ueki and Thomas Kruse and Weisser, {Melanie Bianca} and Sundell, {Gustav N} and Larsen, {Marie Sofie Yoo} and Mendez, {Blanca Lopez} and Jenkins, {Nicole P} and Garvanska, {Dimitriya H} and Lauren Cressey and Gang Zhang and Norman Davey and Guillermo Montoya and Ylva Ivarsson and Kettenbach, {Arminja N} and Jakob Nilsson",

year = "2019",

month = dec,

day = "19",

doi = "10.1016/j.molcel.2019.08.029",

language = "English",

journal = "Molecular Cell",

issn = "1097-2765",

publisher = "Cell Press",

}

TY - JOUR

T1 - A Consensus Binding Motif for the PP4 Protein Phosphatase

AU - Ueki, Yumi

AU - Kruse, Thomas

AU - Weisser, Melanie Bianca

AU - Sundell, Gustav N

AU - Larsen, Marie Sofie Yoo

AU - Mendez, Blanca Lopez

AU - Jenkins, Nicole P

AU - Garvanska, Dimitriya H

AU - Cressey, Lauren

AU - Zhang, Gang

AU - Davey, Norman

AU - Montoya, Guillermo

AU - Ivarsson, Ylva

AU - Kettenbach, Arminja N

AU - Nilsson, Jakob

PY - 2019/12/19

Y1 - 2019/12/19

N2 - Dynamic protein phosphorylation constitutes a fundamental regulatory mechanism in all organisms. Phosphoprotein phosphatase 4 (PP4) is a conserved and essential nuclear serine and threonine phosphatase. 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 thoroughly characterize a general PP4 consensus-binding motif, the FxxP motif. X-ray crystallography studies reveal that FxxP motifs bind to a conserved pocket in the PP4 regulatory subunit PPP4R3. Systems-wide in silico searches integrated with proteomic analysis of PP4 interacting proteins allow us to identify numerous FxxP motifs in proteins controlling a range of fundamental cellular processes. We identify an FxxP motif in the cohesin release factor WAPL and show that this regulates WAPL phosphorylation status and is required for efficient cohesin release. Collectively our work uncovers basic principles of PP4 specificity with broad implications for understanding phosphorylation-mediated signaling in cells.

AB - Dynamic protein phosphorylation constitutes a fundamental regulatory mechanism in all organisms. Phosphoprotein phosphatase 4 (PP4) is a conserved and essential nuclear serine and threonine phosphatase. 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 thoroughly characterize a general PP4 consensus-binding motif, the FxxP motif. X-ray crystallography studies reveal that FxxP motifs bind to a conserved pocket in the PP4 regulatory subunit PPP4R3. Systems-wide in silico searches integrated with proteomic analysis of PP4 interacting proteins allow us to identify numerous FxxP motifs in proteins controlling a range of fundamental cellular processes. We identify an FxxP motif in the cohesin release factor WAPL and show that this regulates WAPL phosphorylation status and is required for efficient cohesin release. Collectively our work uncovers basic principles of PP4 specificity with broad implications for understanding phosphorylation-mediated signaling in cells.

U2 - 10.1016/j.molcel.2019.08.029

DO - 10.1016/j.molcel.2019.08.029

M3 - Journal article

C2 - 31585692

SN - 1097-2765

JO - Molecular Cell

JF - Molecular Cell

ER -

A Consensus Binding Motif for the PP4 Protein Phosphatase

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