Serine/threonine-protein kinase PLK3

Definition:

Serine/threonine-protein kinase involved in cell cycle regulation, response to stress and Golgi disassembly. Polo-like kinases act by binding and phosphorylating proteins are that already phosphorylated on a specific motif recognized by the POLO box domains. Phosphorylates ATF2, BCL2L1, CDC25A, CDC25C, CHEK2, HIF1A, JUN, p53/TP53, p73/TP73, PTEN, TOP2A and VRK1. Involved in cell cycle regulation: required for entry into S phase and cytokinesis. Phosphorylates BCL2L1, leading to regulate the G2 checkpoint and progression to cytokinesis during mitosis. Plays a key role in response to stress: rapidly activated upon stress stimulation, such as ionizing radiation, reactive oxygen species (ROS), hyperosmotic stress, UV irradiation and hypoxia. Involved in DNA damage response and G1/S transition checkpoint by phosphorylating CDC25A, p53/TP53 and p73/TP73. Phosphorylates p53/TP53 in response to reactive oxygen species (ROS), thereby promoting p53/TP53-mediated apoptosis. Phosphorylates CHEK2 in response to DNA damage, promoting the G2/M transition checkpoint. Phosphorylates the transcription factor p73/TP73 in response to DNA damage, leading to inhibit p73/TP73-mediated transcriptional activation and pro-apoptotic functions. Phosphorylates HIF1A and JUN is response to hypoxia. Phosphorylates ATF2 following hyperosmotic stress in corneal epithelium. Also involved in Golgi disassembly during the cell cycle: part of a MEK1/MAP2K1-dependent pathway that induces Golgi fragmentation during mitosis by mediating phosphorylation of VRK1. May participate in endomitotic cell cycle, a form of mitosis in which both karyokinesis and cytokinesis are interrupted and is a hallmark of megakaryocyte differentiation, via its interaction with CIB1.

References:

[1]. Dazhong Xu, et al. Regulation of PTEN stability and activity by Plk3. J Biol Chem. 2010 Dec 17;285(51):39935-42. [Content Brief]

[2]. Ling Wang, et al. Activation of Polo-like kinase 3 by hypoxic stresses. J Biol Chem. 2008 Sep 19;283(38):25928-35. [Content Brief]

[3]. Wendy C Zimmerman, et al. Polo-like kinase 3 is required for entry into S phase. Proc Natl Acad Sci U S A. 2007 Feb 6;104(6):1847-52. [Content Brief]

[4]. B Ouyang, et al. The physical association and phosphorylation of Cdc25C protein phosphatase by Prk. Oncogene. 1999 Oct 28;18(44):6029-36. [Content Brief]

[5]. El Mustapha Bahassi, et al. Cdc25C phosphorylation on serine 191 by Plk3 promotes its nuclear translocation. Oncogene. 2004 Apr 8;23(15):2658-63. [Content Brief]

[6]. Ling Wang, et al. Stress-induced c-Jun activation mediated by Polo-like kinase 3 in corneal epithelial cells. J Biol Chem. 2007 Nov 2;282(44):32121-7. [Content Brief]

[7]. Masato Iida, et al. Plk3 phosphorylates topoisomerase IIalpha at Thr(1342), a site that is not recognized by Plk1. Biochem J. 2008 Apr 1;411(1):27-32. [Content Brief]

[8]. Meixiang Sang, et al. Plk3 inhibits pro-apoptotic activity of p73 through physical interaction and phosphorylation. Genes Cells. 2009 Jul;14(7):775-88. [Content Brief]

[9]. Jianfang Wang, et al. Bcl-xL phosphorylation at Ser49 by polo kinase 3 during cell cycle progression and checkpoints. Cell Signal. 2011 Dec;23(12):2030-8. [Content Brief]

[10]. Suqing Xie, et al. MEK1-induced Golgi dynamics during cell cycle progression is partly mediated by Polo-like kinase-3. Oncogene. 2004 May 6;23(21):3822-9. [Content Brief]

[11]. B Ouyang, et al. Human Prk is a conserved protein serine/threonine kinase involved in regulating M phase functions. J Biol Chem. 1997 Nov 7;272(45):28646-51. [Content Brief]

[12]. Qin Ruan, et al. Polo-like kinase 3 is Golgi localized and involved in regulating Golgi fragmentation during the cell cycle. Exp Cell Res. 2004 Mar 10;294(1):51-9. [Content Brief]

[13]. Ling Wang, et al. Hyperosmotic stress-induced ATF-2 activation through Polo-like kinase 3 in human corneal epithelial cells. J Biol Chem. 2011 Jan 21;286(3):1951-8. [Content Brief]

[14]. S Xie, et al. Plk3 functionally links DNA damage to cell cycle arrest and apoptosis at least in part via the p53 pathway. J Biol Chem. 2001 Nov 16;276(46):43305-12. [Content Brief]

[15]. C W Conn, et al. Incomplete cytokinesis and induction of apoptosis by overexpression of the mammalian polo-like kinase, Plk3. Cancer Res. 2000 Dec 15;60(24):6826-31. [Content Brief]

[16]. S Xie, et al. Reactive oxygen species-induced phosphorylation of p53 on serine 20 is mediated in part by polo-like kinase-3. J Biol Chem. 2001 Sep 28;276(39):36194-9. [Content Brief]

[17]. El Mustapha Bahassi, et al. Mammalian Polo-like kinase 3 (Plk3) is a multifunctional protein involved in stress response pathways. Oncogene. 2002 Sep 26;21(43):6633-40. [Content Brief]

[18]. David L Myer, et al. Absence of polo-like kinase 3 in mice stabilizes Cdc25A after DNA damage but is not sufficient to produce tumors. Mutat Res. 2011 Sep 1;714(1-2):1-10. [Content Brief]

[19]. Dazhong Xu, et al. Plk3 functions as an essential component of the hypoxia regulatory pathway by direct phosphorylation of HIF-1alpha. J Biol Chem. 2010 Dec 10;285(50):38944-50. [Content Brief]

[20]. Qi Wang, et al. Cell cycle arrest and apoptosis induced by human Polo-like kinase 3 is mediated through perturbation of microtubule integrity. Mol Cell Biol. 2002 May;22(10):3450-9. [Content Brief]

[21]. John C Kostyak, et al. Calcium- and integrin-binding protein 1 regulates endomitosis and its interaction with Polo-like kinase 3 is enhanced in endomitotic Dami cells. PLoS One. 2011 Jan 14;6(1):e14513. [Content Brief]

[22]. Inmaculada López-Sánchez, et al. Plk3 interacts with and specifically phosphorylates VRK1 in Ser342, a downstream target in a pathway that induces Golgi fragmentation. Mol Cell Biol. 2009 Mar;29(5):1189-201. [Content Brief]

[23]. Ning Jiang, et al. Polo box domain of Plk3 functions as a centrosome localization signal, overexpression of which causes mitotic arrest, cytokinesis defects, and apoptosis. J Biol Chem. 2006 Apr 14;281(15):10577-82. [Content Brief]

[24]. El Mustapha Bahassi, et al. Priming phosphorylation of Chk2 by polo-like kinase 3 (Plk3) mediates its full activation by ATM and a downstream checkpoint in response to DNA damage. Mutat Res. 2006 Apr 11;596(1-2):166-76. [Content Brief]

[25]. Meghna U Naik, et al. Calcium- and integrin-binding protein 1 regulates microtubule organization and centrosome segregation through polo like kinase 3 during cell cycle progression. Int J Biochem Cell Biol. 2011 Jan;43(1):120-9. [Content Brief]

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