Phosphorylation of cohesin by PLK1 at centromeres

Stable Identifier
R-HSA-1638803
Type
Reaction [transition]
Species
Homo sapiens
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Prior to anaphase onset, sister-chromatids are held together by cohesin complexes distributed along chromosomal arms and at centromeres. In prometaphase, PLK1, likely recruited to cohesin complexes by binding to CDK1-phosphorylated CDCA5 (Sororin) (Zhang et al. 2011), phosphorylates cohesin subunits STAG2 (SA2) and RAD21 (Hauf et al. 2005). PLK1-mediated phosphorylation of cohesin subunits at centromeres is counteracted by the phosphatase activity of PP2A complex (containing the regulatory subunit B56 i.e. PPP2R5), which is recruited to the kinetochore by shugoshin proteins, SGOL1 and SGOL2 (Kitajima et al. 2006). Therefore, while cohesin complexes dissociate from chromosomal arms in prometaphase (Hauf et al. 2001), they remain bound to centromeres until anaphase onset (Hauf et al. 2001, Hauf et al. 2005, Kitajima et al. 2006). When separase is activated after its inhibitor securin is degraded by APC/C at the onset of anaphase, RAD21 is cleaved by separase. Phosphorylation of RAD21 by PLK1 facilitates subsequent cleavage of RAD21 by separase (Hauf et al. 2005). There are several potential PLK1 phosphorylation sites in STAG2 and RAD21, but the exact positions of in vivo phosphorylation of STAG2 and RAD21 by PLK1 have not been explicitly established (Hauf et al. 2005).

Literature References
PubMed ID Title Journal Year
11509732 Cohesin cleavage by separase required for anaphase and cytokinesis in human cells

Peters, JM, Hauf, S, Waizenegger, IC

Science 2001
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
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
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Catalyst Activity

protein serine/threonine kinase activity of PLK1 [cytosol]

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