A highly conserved pocket on PP2A-B56 is required for hSgo1 binding and cohesion protection during mitosis
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A highly conserved pocket on PP2A-B56 is required for hSgo1 binding and cohesion protection during mitosis. / Ueki, Yumi; Hadders, Michael A; Weisser, Melanie B; Nasa, Isha; Sotelo-Parrilla, Paula; Cressey, Lauren E; Gupta, Tanmay; Hertz, Emil P T; Kruse, Thomas; Montoya, Guillermo; Jeyaprakash, A. Arockia; Kettenbach, Arminja; Lens, Susanne M A; Nilsson, Jakob.
In: EMBO Reports, Vol. 22, No. 7, e52295, 2021.Research output: Contribution to journal › Journal article › peer-review
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TY - JOUR
T1 - A highly conserved pocket on PP2A-B56 is required for hSgo1 binding and cohesion protection during mitosis
AU - Ueki, Yumi
AU - Hadders, Michael A
AU - Weisser, Melanie B
AU - Nasa, Isha
AU - Sotelo-Parrilla, Paula
AU - Cressey, Lauren E
AU - Gupta, Tanmay
AU - Hertz, Emil P T
AU - Kruse, Thomas
AU - Montoya, Guillermo
AU - Jeyaprakash, A. Arockia
AU - Kettenbach, Arminja
AU - Lens, Susanne M A
AU - Nilsson, Jakob
PY - 2021
Y1 - 2021
N2 - The shugoshin proteins are universal protectors of centromeric cohesin during mitosis and meiosis. The binding of human hSgo1 to the PP2A-B56 phosphatase through a coiled-coil (CC) region mediates cohesion protection during mitosis. Here we undertook a structure function analysis of the PP2A-B56-hSgo1 complex, revealing unanticipated aspects of complex formation and function. We establish that a highly conserved pocket on the B56 regulatory subunit is required for hSgo1 binding and cohesion protection during mitosis in human somatic cells. Consistent with this, we show that hSgo1 blocks the binding of PP2A-B56 substrates containing a canonical B56 binding motif. We find that PP2A-B56 bound to hSgo1 dephosphorylates Cdk1 sites on hSgo1 itself to modulate cohesin interactions. Collectively our work provides important insight into cohesion protection during mitosis.
AB - The shugoshin proteins are universal protectors of centromeric cohesin during mitosis and meiosis. The binding of human hSgo1 to the PP2A-B56 phosphatase through a coiled-coil (CC) region mediates cohesion protection during mitosis. Here we undertook a structure function analysis of the PP2A-B56-hSgo1 complex, revealing unanticipated aspects of complex formation and function. We establish that a highly conserved pocket on the B56 regulatory subunit is required for hSgo1 binding and cohesion protection during mitosis in human somatic cells. Consistent with this, we show that hSgo1 blocks the binding of PP2A-B56 substrates containing a canonical B56 binding motif. We find that PP2A-B56 bound to hSgo1 dephosphorylates Cdk1 sites on hSgo1 itself to modulate cohesin interactions. Collectively our work provides important insight into cohesion protection during mitosis.
U2 - 10.15252/embr.202052295
DO - 10.15252/embr.202052295
M3 - Journal article
C2 - 33973335
VL - 22
JO - E M B O Reports
JF - E M B O Reports
SN - 1469-221X
IS - 7
M1 - e52295
ER -
ID: 261517491