Disease relevance of PLK2

• Silencing occurs with very high frequency in Burkitt lymphoma (BL) but is also detected in B-cell neoplasms of other types and is associated with aberrant cytosine methylation in the CpG island located at the 5' end of the SNK/PLK2 gene [1].
• Silencing is specific to malignant B cells because SNK/PLK2 was unmethylated (and expressed) in primary B lymphocytes, in EBV-immortalized B lymphoblastoid cell lines (LCLs), and in adenocarcinomas (of the breast) and squamous-cell carcinomas (of the head and neck) [1].
• More recent evidence reveals a novel function for Plk2 in mediating apoptosis in high grade B lymphomas [2].
• During the cisplatin-induced apoptosis in human neuroblastoma SH-SY5Y cells, the expression level of Plk1 was significantly decreased both at mRNA and protein levels, whereas cisplatin treatment caused a remarkable stabilization of p53 [3].
• These results support a model for transformation caused by HPV-16 where bypass of arrest and tetraploidy are separable consequences of p53 loss with Plk1 required only for the latter effect [4].

High impact information on PLK2

• The Plk1 target Kizuna stabilizes mitotic centrosomes to ensure spindle bipolarity [5].
• Here, we identify a novel centrosomal substrate of Plk1, Kizuna (Kiz), depletion of which causes fragmentation and dissociation of the pericentriolar material from centrioles at prometaphase, resulting in multipolar spindles [5].
• Effect of RNA silencing of polo-like kinase-1 (PLK1) on apoptosis and spindle formation in human cancer cells [6].
• Over expression of other mitotic kinases (Polo-like kinase 1 and Aurora-B) also causes multinucleation and concomitant increases in centrosome numbers [7].
• Injection of anti-Plk1 antibodies (Plk1+) at various stages of the cell cycle had no effect on the kinetics of DNA replication but severely impaired the ability of cells to divide [8].

Chemical compound and disease context of PLK2

• We used phosphorothioate antisense oligonucleotides (ASO) targeted against Plk1, together with paclitaxel, carboplatin, and Herceptin, for the treatment of breast cancer cells to identify conditions for enhanced drug sensitivity [9].
• Here we report a quick functional analysis of two mammalian serine/threonine kinases, a serum inducible kinase (Snk) and Homo sapiens hepatoma protein kinase (HsHPK), using Drosophila eye as a model system [10].

Biological context of PLK2

• Ectopic expression of Snk/Plk2 in BL cells resulted in apoptosis, a potential mechanistic basis underlying the strong selective pressure for abrogation of Snk/Plk2 function in B-cell neoplasia [1].
• Serum-inducible kinase (SNK) is a member of polo-like kinases that serve as regulators of multiple events during cell division [11].
• The half-life of SNK is increased in HeLa cells that down-regulated hVPS18 by lentivirus-mediated small hairpin RNA interference [11].
• Rapid changes in the activity and abundance of SNK were reported after the serum stimulation and after the activation of synaptic transmission in the brain [11].
• AX7503 labeling on Plk1 and Plk3 was found to occur on a conserved ATP binding site residue [12].

Anatomical context of PLK2

• Transcriptional silencing of Polo-like kinase 2 (SNK/PLK2) is a frequent event in B-cell malignancies [1].
• Expression of Snk/Plk2 in BL cell lines was restored by demethylating agents [1].
• The ectopically overexpressed Plk1 was co-localized with the endogenous p53 in mammalian cell nucleus, as shown by confocal laser microscopy [3].
• Here we found for the first time that Plk1 physically binds to the tumor suppressor p53 in mammalian cultured cells, and inhibits its transactivation activity as well as its pro-apoptotic function [3].
• Polo-like kinase 1 (Plk1) is one of the serine/threonine kinases involved in various mitotic processes, such as centrosome maturation and chromosome segregation [13].

Associations of PLK2 with chemical compounds

• In COS cells, Plk2 and Plk3 interact with spine-associated Rap guanosine triphosphatase-activating protein (SPAR), a regulator of actin dynamics and dendritic spine morphology, leading to its degradation through the ubiquitin-proteasome system [14].
• Although transcription of the SNK gene was also regulated by tunicamycin, etoposide, or staurosporine, FK506 did not show any effects on these regulations [15].
• Screening of Domain-specific Target Proteins of Polo-like Kinase 1: Construction and Application of Centrosome/Kinetochore-specific Targeting Peptide [16].
• Small interfering RNA (siRNA)-mediated Snk/Plk2 silencing in the presence of the mitotic poisons paclitaxel (Taxol) or nocodazole significantly increased apoptosis, similar to p53 mutations, which confer paclitaxel sensitivity [17].
• Influence of chk1 and plk1 silencing on radiation- or cisplatin-induced cytotoxicity in human malignant cells [18].

Regulatory relationships of PLK2

• The vector-based RNAi approach was used to evaluate the role of the p53 pathway in Plk1 depletion-induced apoptosis in cancer cells with different p53 backgrounds [19].

Other interactions of PLK2

• Using the yeast two-hybrid screening, we identify SNK as a candidate substrate of hVPS18 [11].
• Epigenetic inactivation of Plk2 via aberrant CpG methylation in the transcriptional regulatory elements of the gene is a common event in B cell neoplasia, whereas epigenetic inactivation of Plk3 is exceedingly rare in lymphomas [2].
• The Plk family genes are also differentially regulated in stressed cells; for example, when DNA-damaging agents are added to cycling cells, Plk1 expression decreases, but Plk2 and Plk3 expression increases [20].
• Induction of Plk2 in hippocampal neurons eliminates SPAR protein, depletes a core postsynaptic scaffolding molecule (PSD-95), and causes loss of mature dendritic spines and synapses [14].

Analytical, diagnostic and therapeutic context of PLK2

• Systematic immunoprecipitation analyses using a series of deletion mutants of p53 revealed that a sequence-specific DNA-binding region of p53 is required and sufficient for the physical interaction with Plk1 [3].
• The expression of Plk1 was analyzed by reverse transcriptional PCR and a tissue array using immunohistochemical staining method in gastric adenocarcinoma tissues [13].
• Interestingly, in a human xenograft experiment using MDA-MB-435 cells, the combination of Plk1 ASOs with paclitaxel led to synergistic reduction of tumor growth after 3 weeks of treatment compared with either agent alone [9].
• METHODS: PLK1 expression was determined in 160 gastric carcinoma patients by immunohistochemistry and compared with p53 expression and the proliferating cell nuclear antigen-labeling index (PCNA-LI) to evaluate the effect of PLK1 on tumor progression [21].
• We have generated mice deficient in Plk2 by gene targeting [22].

References