Reactome | Phosphorylation of cohesin by PLK1 at centromeres

Phosphorylation of cohesin by PLK1 at centromeres

Stable Identifier

R-HSA-1638803

Type

Reaction [transition]

Species

Homo sapiens

Compartment

chromosome, centromeric region, cytosol

ReviewStatus

4/5

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Phosphorylation of cohesin by PLK1 at centromeres

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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