PP2A-B56 dephosphorylates centromeric cohesin

Stable Identifier
Reaction [transition]
Homo sapiens
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PLK1-mediated phosphorylation of the STAG2 subunit of centromeric cohesin (Hauf et al. 2005) is counteracted by the kinetochore PP2A phosphatase, containing the 56 kDa regulatory B subunit (PP2A-B56 i.e. PP2A-PPP2R5). PP2A-B56 is recruited to the centromeric cohesin complex by shugoshin proteins (SGOL1 and SGOL2) (Kitajima et al. 2006), which are also kinetochore constituents (Cheeseman and Desai 2008). SGOL1 localization to centromeres is sustained by the interaction with histone H2A possessing the phosphorylation of T120 which is introduced by the protein kinase BUB1, and heterochromatin protein HP1 (Kitajima et al. 2005, Kawashima et al. 2010, Yamagishi et al. 2008). Shugoshin- and PP2A-B56-regulated dephosphorylation of centromeric STAG2 ensures that the cohesin complex remains bound to centromeres throughout prometaphase and metaphase, thereby preventing premature separation of sister chromatids (Salic et al. 2004, Kitajima et al. 2004, Kitajima et al. 2005, Kitajima et al. 2006).

Literature References
PubMed ID Title Journal Year
15723797 Human Bub1 defines the persistent cohesion site along the mitotic chromosome by affecting Shugoshin localization

Hauf, S, Watanabe, Y, Ohsugi, M, Yamamoto, T, Kitajima, TS

Curr. Biol. 2005
19965387 Phosphorylation of H2A by Bub1 prevents chromosomal instability through localizing shugoshin

Honda, T, Yamagishi, Y, Kawashima, SA, Ishiguro, K, Watanabe, Y

Science 2010
16541025 Shugoshin collaborates with protein phosphatase 2A to protect cohesin

Natsume, T, Ishiguro, K, Watanabe, Y, Kawashima, SA, Kitajima, TS, Iemura, S, Sakuno, T

Nature 2006
15339662 Vertebrate shugoshin links sister centromere cohesion and kinetochore microtubule stability in mitosis

Mitchison, TJ, Waters, JC, Salic, A

Cell 2004
14730319 The conserved kinetochore protein shugoshin protects centromeric cohesion during meiosis

Kawashima, SA, Watanabe, Y, Kitajima, TS

Nature 2004
18097444 Molecular architecture of the kinetochore-microtubule interface

Cheeseman, IM, Desai, A

Nat Rev Mol Cell Biol 2008
15737063 Dissociation of cohesin from chromosome arms and loss of arm cohesion during early mitosis depends on phosphorylation of SA2

Roitinger, E, Mechtler, K, Dittrich, CM, Peters, JM, Hauf, S, Koch, B

PLoS Biol 2005
18716626 Heterochromatin links to centromeric protection by recruiting shugoshin

Yamagishi, Y, Watanabe, Y, Sakuno, T, Shimura, M

Nature 2008
Catalyst Activity

protein serine/threonine phosphatase activity of p-STAG2,RAD21-Ac-Cohesin:PDS5:p-CDCA5:WAPAL:Sister Centromeres:Kinetochores:Microtubules [chromosome, centromeric region]

Orthologous Events
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