Reactome | Regulation of PLK1 Activity at G2/M Transition

Regulation of PLK1 Activity at G2/M Transition

Stable Identifier

R-HSA-2565942

DOI

10.3180/R-HSA-2565942.4

Type

Pathway

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

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Regulation of PLK1 Activity at G2/M Transition

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The kinase activity of PLK1 is required for cell cycle progression as PLK1 phosphorylates and regulates a number of cellular proteins during mitosis. Centrosomic AURKA (Aurora A kinase), catalytically activated through AJUBA facilitated autophosphorylation on threonine residue T288 at G2/M transition (Hirota et al. 2003), activates PLK1 on centrosomes by phosphorylating threonine residue T210 of PLK1, critical for PLK1 activity (Jang et al. 2002), in the presence of BORA (Macurek et al. 2008, Seki et al. 2008). Once activated, PLK1 phosphorylates BORA and targets it for ubiquitination mediated degradation by SCF-beta-TrCP ubiquitin ligases. Degradation of BORA is thought to allow PLK1 to interact with other substrates (Seki, Coppinger, Du et al. 2008, Seki et al. 2008).

The interaction of PLK1 with OPTN (optineurin) provides a negative-feedback mechanism for regulation of PLK1 activity. Phosphorylated PLK1 binds and phosphorylates OPTN associated with the Golgi membrane GTPase RAB8, promoting dissociation of OPTN from Golgi and translocation of OPTN to the nucleus. Phosphorylated OPTN facilitates the mitotic phosphorylation of the myosin phosphatase subunit PPP1R12A (MYPT1) and myosin phosphatase activation (Kachaner et al. 2012). The myosin phosphatase complex dephosphorylates threonine residue T210 of PLK1 and inactivates PLK1 (Yamashiro et al. 2008).

Literature References

PubMed ID	Title	Journal	Year
18566290	Bora and the kinase Aurora a cooperatively activate the kinase Plk1 and control mitotic entry Seki, A, Coppinger, JA, Yates, JR, Jang, CY, Fang, G	Science	2008
13678582	Aurora-A and an interacting activator, the LIM protein Ajuba, are required for mitotic commitment in human cells Hirota, T, Hatakeyama, K, Nitta, M, Sasayama, T, Saya, H, Kunitoku, N, Zhang, D, Marumoto, T	Cell	2003
22365832	Plk1-dependent phosphorylation of optineurin provides a negative feedback mechanism for mitotic progression Laplantine, E, Bennett, KL, Superti-Furga, G, Weil, R, Kachaner, D, Israel, A, Bauch, A, Filipe, J	Mol. Cell	2012
18615013	Polo-like kinase-1 is activated by aurora A to promote checkpoint recovery Clouin, C, Medema, RH, Taylor, SS, Freire, R, Lampson, MA, Klompmaker, R, Lim, D, Yaffe, MB, Lindqvist, A, Mac?rek, L	Nature	2008
12207013	Phosphorylation of threonine 210 and the role of serine 137 in the regulation of mammalian polo-like kinase Erikson, RL, Ma, S, Jang, YJ, Terada, Y	J. Biol. Chem.	2002
18477460	Myosin phosphatase-targeting subunit 1 regulates mitosis by antagonizing polo-like kinase 1 Goto, H, Kaibuchi, K, Hartshorne, DJ, Totsukawa, G, Matsumura, F, Yamashiro, S, Ito, M, Yamakita, Y	Dev. Cell	2008
18378770	Plk1- and beta-TrCP-dependent degradation of Bora controls mitotic progression Seki, A, Coppinger, JA, Yates, JR, Jang, CY, Fang, G, Du, H	J. Cell Biol.	2008