Distinct kinetics of serine and threonine dephosphorylation are essential for mitosis
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Distinct kinetics of serine and threonine dephosphorylation are essential for mitosis. / Hein, Jamin B; Hertz, Emil P T; Garvanska, Dimitriya H; Kruse, Thomas; Nilsson, Jakob.
In: Nature Cell Biology, Vol. 19, 2017, p. 1433-1440.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Distinct kinetics of serine and threonine dephosphorylation are essential for mitosis
AU - Hein, Jamin B
AU - Hertz, Emil P T
AU - Garvanska, Dimitriya H
AU - Kruse, Thomas
AU - Nilsson, Jakob
PY - 2017
Y1 - 2017
N2 - Protein phosphatase 2A (PP2A) in complex with B55 regulatory subunits reverses cyclin-dependent kinase 1 (Cdk1) phosphorylations at mitotic exit. Interestingly, threonine and serine residues phosphorylated by Cdk1 display distinct phosphorylation dynamics, but the biological significance remains unexplored. Here we demonstrate that the phosphothreonine preference of PP2A-B55 provides an essential regulatory element of mitotic exit. To allow rapid activation of the anaphase-promoting complex/cyclosome (APC/C) co-activator Cdc20, inhibitory phosphorylation sites are conserved as threonines while serine substitutions delay dephosphorylation and Cdc20 activation. Conversely, to ensure timely activation of the interphase APC/C co-activator Cdh1, inhibitory phosphorylation sites are conserved as serines, and threonine substitutions result in premature Cdh1 activation. Furthermore, rapid translocation of the chromosomal passenger complex to the central spindle is prevented by mutation of a single phosphorylated threonine to serine in inner centromere protein (INCENP), leading to failure of cytokinesis. Altogether, the findings of our work reveal that the inherent residue preference of a protein phosphatase can provide temporal regulation in biological processes.
AB - Protein phosphatase 2A (PP2A) in complex with B55 regulatory subunits reverses cyclin-dependent kinase 1 (Cdk1) phosphorylations at mitotic exit. Interestingly, threonine and serine residues phosphorylated by Cdk1 display distinct phosphorylation dynamics, but the biological significance remains unexplored. Here we demonstrate that the phosphothreonine preference of PP2A-B55 provides an essential regulatory element of mitotic exit. To allow rapid activation of the anaphase-promoting complex/cyclosome (APC/C) co-activator Cdc20, inhibitory phosphorylation sites are conserved as threonines while serine substitutions delay dephosphorylation and Cdc20 activation. Conversely, to ensure timely activation of the interphase APC/C co-activator Cdh1, inhibitory phosphorylation sites are conserved as serines, and threonine substitutions result in premature Cdh1 activation. Furthermore, rapid translocation of the chromosomal passenger complex to the central spindle is prevented by mutation of a single phosphorylated threonine to serine in inner centromere protein (INCENP), leading to failure of cytokinesis. Altogether, the findings of our work reveal that the inherent residue preference of a protein phosphatase can provide temporal regulation in biological processes.
KW - Journal Article
U2 - 10.1038/ncb3634
DO - 10.1038/ncb3634
M3 - Journal article
C2 - 29084198
VL - 19
SP - 1433
EP - 1440
JO - Nature Cell Biology
JF - Nature Cell Biology
SN - 1465-7392
ER -
ID: 186123343