Disease relevance of Plk1

• These results establish LFM-A13 as a small molecule inhibitor of Plk with in vitro and in vivo anti-proliferative activity against human breast cancer [1].
• The largest open reading frame of the Plk1 cDNA encodes a protein of 68,254 daltons, and a protein of this size is detected by immunoblotting of HeLa cell extracts with monoclonal antibodies raised against the C-terminal part of Plk1 expressed in Escherichia coli [2].
• Within the precommitment period of murine erythroleukemia cell terminal differentiation, most of the poly(A) tail is lost from the STPK13 mRNA, but the body of the mRNA remains unchanged in abundance; this poly(A) loss does not occur in mutant erythroleukemia cells that fail to commit to terminal differentiation [3].
• Novel oncolytic adenovirus selectively targets tumor-associated polo-like kinase 1 and tumor cell viability [4].
• METHODS: HeLa S3 cervical and A549 lung cancer cell lines were transfected with plasmids containing U6 promoter-driven shRNAs against human PLK1 or control (parental or scrambled) plasmids [5].

High impact information on Plk1

• We demonstrate that FKH-TFs regulate expression of mitotic genes such as cyclin B and polo-like kinase (Plk) [6].
• These results indicate that Plk and PKA regulate mitosis progression by controlling APC activity [7].
• PKA is superior to Plk in its regulation of APC, and Plk activity peaks whereas PKA activity is falling at metaphase [7].
• INCENP depletion disrupts Plk1 localization specifically at the kinetochore [8].
• The human Polo-like kinase 1 (PLK1) and its functional homologues that are present in other eukaryotes have multiple, crucial roles in meiotic and mitotic cell division [9].

Chemical compound and disease context of Plk1

• Moreover, selective targeting of plk1 or chk1 in tumor xenografts of mice by oncolytic adenovirus mutants demonstrated potent anti-tumoral efficacy in the presence of low dose cisplatin [10].

Biological context of Plk1

• Plk1-depleted cells enter mitosis after a short delay, accumulate in a preanaphase state, and subsequently often die by apoptosis [11].
• Phosphorylation of BR-N1 with Plk1 recapitulated the electrophoretic mobility change as seen in BR-N1 isolated from M phase cells [12].
• In Plk1-depleted cells spindles may not be able to create enough tension across sister kinetochores to stabilize microtubule-kinetochore interactions and to silence the spindle checkpoint [11].
• RESULTS: We have analyzed Plk1 functions in synchronized mammalian cells by RNA interference (RNAi) [11].
• Due to close sequence homology to human Slk and Xenopus laevis xPlkk1, two polo-like kinase kinases, we investigated whether Stk10 might also play a role as a Plk1 activator [13].

Anatomical context of Plk1

• Spindles in Plk1-depleted cells lack focused poles and are not associated with centrosomes [11].
• We have confirmed the specific pattern of immuno-localisation seen in fixed preparations by observing the distribution of Plk1 tagged with green fluorescent protein in living oocytes [14].
• Plk1 disappeared at the spindle region when microtubule formation was inhibited by colchicine or staurosporine, while it was concentrated as several dots in the cytoplasm after taxol treatment [15].
• Cell cycle dependent expression of Plk1 in synchronized porcine fetal fibroblasts [16].
• To define the role of Plk1 in germ cell development, we have examined its expression in murine gonads by in situ hybridization [17].

Associations of Plk1 with chemical compounds

• Experiments with monopolar spindles that are induced by the kinesin inhibitor Monastrol indicate that Plk1 is required for the assembly of spindles that are able to generate poleward pulling forces [11].
• Phosphorylated hamartin interacts with Plk1 independent of tuberin with all three proteins present in a complex [18].
• Among 41 phosphorothioate antisense oligodeoxynucleotides tested, the 20-mer JWG2000 strongly inhibited expression of Plk1 in cultured A549 cells, leading to loss of cell viability, and exhibited anti-tumor activity in nude mice A549 xenograft [19].
• After administration of Dox knockdown of Plk1 expression was observed correlating to a significant inhibition of tumor growth [20].
• For this purpose inducible RNAi vectors containing tetracycline (Tet)-responsive derivatives of the H1 promoter for the conditional expression of short hairpin RNA (shRNA) were used to target human polo-like kinase 1 (Plk1), which is overexpressed in a broad spectrum of human tumors [20].

Other interactions of Plk1

• Reduced hepatoblast mitosis was associated with decreased protein levels of the Polo-like kinase 1 and Aurora B kinase, which phosphorylate regulatory proteins essential for orchestrating mitosis and cytokinesis [21].
• Polo-like kinase (Plk) is a cell cycle-regulated, cyclin-independent serine/threonine protein kinase [22].

Analytical, diagnostic and therapeutic context of Plk1

• In this experiment, the changes in Plk1 expression were detected in mouse oocytes through Western blotting [15].
• The subcellular localization of Plk1 during oocyte meiotic maturation, fertilization, and early cleavage as well as after antibody microinjection or microtubule assembly disturbance was studied by confocal microscopy [15].
• The expression levels of Plk1 mRNA at various points of the cell cycle in synchronized porcine fetal fibroblasts were analyzed by both RT-PCR and the ribonuclease protection assay [16].
• Using EGFP-tagged initiator proteins and immunofluorescence techniques we found that most of the ORC and the MCM subunits are localised at centrosomes and are colocalised with the polo-like protein kinase, Plk1 [23].
• In addition, Plk1 siRNA inhibited colony formation in soft agar and tumorigenesis in a HT1080 xenograft model in a dose-dependent manner [24].

References