A highly conserved pocket on PP2A‐B56 is required for hSgo1 binding and cohesion protection during mitosis |
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| Authors: | Yumi Ueki,Michael A Hadders,Melanie B Weisser,Isha Nasa,Paula Sotelo‐ Parrilla,Lauren E Cressey,Tanmay Gupta,Emil P T Hertz,Thomas Kruse,Guillermo Montoya,A Arockia Jeyaprakash,Arminja Kettenbach,Susanne M A Lens,Jakob Nilsson |
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| Affiliation: | 1. The Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Science, University of Copenhagen, Copenhagen Denmark ; 2. Oncode Institute and Center for Molecular Medicine, University Medical Center Utrech, Utrecht University, Utrecht The Netherlands ; 3. Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth College, Hanover NH, USA ; 4. Wellcome Center for Cell Biology, University of Edinburgh, Edinburgh UK |
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| Abstract: | 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. |
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| Keywords: | cohesin, mitosis, phosphatase, PP2A‐ B56, shugoshin |
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