Ask about this productRelated genes to: PLK4 antibody
- Gene:
- PLK4 NIH gene
- Name:
- polo like kinase 4
- Previous symbol:
- STK18
- Synonyms:
- Sak
- Chromosome:
- 4q28.1
- Locus Type:
- gene with protein product
- Date approved:
- 1998-12-09
- Date modifiied:
- 2016-01-22
Related products to: PLK4 antibody
Related articles to: PLK4 antibody
- Centrosome amplification is frequently associated with chromosomal instability and tumor progression, but how cells coordinate centriole assembly with the control of centrosome numbers and quality remains poorly understood. TIAM1 is a RAC1 guanine nucleotide exchange factor previously implicated in centrosome-associated signaling and βTrCP-dependent control of PLK4 abundance. Here, we examined how Tiam1 regulates autophagy-lysosome homeostasis in mouse embryonic fibroblasts induced to overexpress PLK4. In contrast to a previous model in which Tiam1 loss promotes productive centriole overduplication, we found, by super-resolution imaging and expansion microscopy, an abnormal distribution of PLK4 on the centrioles centriole-associated structures following TIAM1 depletion, suggesting that TIAM1 may support the organization or maturation of centrioles. TIAM1 depletion also resulted in increased LC3B-positive puncta and enlarged LAMP1-positive compartments, but this was not accompanied by increased LC3B-II accumulation after bafilomycin A1 treatment. These findings suggest that TIAM1 may act at the interface between centriole assembly and endolysosomal/autolysosomal organization, linking TIAM1 to lysosome-associated centrosome quality-control pathways. - Source: PubMed
Publication date: 2026/07/03
Coelho Paula AYu ChenrongGlover David M - As a key regulator of centrosome duplication, polo-like kinase 4 (PLK4) is abnormally overexpressed in various tumors and has emerged as an important target for the development of antitumor drugs. In this study, based on the lead compound (PLK4 IC50 = 3.0 μM) previously obtained by our research group, we designed and synthesized 28 novel quinazoline-based PLK4 inhibitors to enhance kinase inhibitory activity using side-chain extension strategies. Among them, compound (PLK4 IC50 < 0.1 nM) exhibited favorable in vitro antiproliferative activity against -amplified MCF-7 breast cancer cells (MCF-7 IC50 = 2.37 ± 0.26 μM) and -amplified neuroblastoma IMR-32 cells (IMR-32 IC50 = 1.28 ± 0.04 μM). Its activity was superior to that of the positive control LCR-263. Further in vitro biological evaluation demonstrated that inhibited the colony formation of MCF-7 cells in a concentration-dependent manner, induced S/G2-phase cell-cycle arrest, and promoted apoptosis. also showed favorable metabolic stability in human liver microsomes, with a half-life of 61.3 min. However, no obvious amplification-dependent cellular selectivity was observed in non-highly amplified A549 cells or normal human embryonic kidney HEK-293T cells. Given the suboptimal selectivity of the in vitro antiproliferative activity, Aurora kinase A, which shares high homology with PLK4, was selected for further evaluation of its selectivity. The IC50 for Aurora A inhibition was determined to be 151.2 nM, indicating that its broader kinase selectivity remains to be established. In summary, is a highly potent biochemical PLK4 inhibitor and provides a useful lead scaffold for further optimization rather than a fully selective cellular candidate at the current stage. - Source: PubMed
Publication date: 2026/08/12
Sun WenqiangQi ZehuiHu NingyuanLiu NianMu ShuyiZhang HaoyuGao ZixuanLuo ZiruiSun YinZhao DongmeiCheng Maosheng - In dividing cells, centrosomes are the primary microtubule-organizing centers and typically duplicate only once per cell division cycle, ensuring that there is just a single centrosome at each mitotic spindle pole. Centrosome amplification presents a paradox: although supernumerary centrosomes can induce chromosomal instability and promote invasive behavior, they may also impede cell proliferation by activating the Hippo-LATS pathway and the PIDDosome-p53 axis. Therefore, cells with supernumerary centrosomes must either tolerate the abnormal centrosome numbers or restore centrosome homeostasis. To identify pathways that allow cell proliferation in the presence of extra centrosomes, we conducted a genome-wide CRISPR/Cas9 screen in mouse embryonic stem cells to identify gene knock-outs that restored cell proliferation following induction of a polo-like kinase 4 (PLK4) transgene. In addition to components of known pathways that respond to supernumerary centrosomes, the screen identified a previously unrecognized Rho GTPase signaling network. Depletion of the RAC1 GTPase-activating protein ARHGAP15 increases autophagic flux, reduces the percentage of cells with supernumerary centrosomes in an ATG16L1-dependent manner, and restores proliferation of cells following PLK4 overexpression. Our findings support a model in which the centrosomal protein CEP170 promotes ARHGEF2-dependent RAC1 activation, enabling RAC1-GTP to interact with ATG16L1 and stimulate autophagy. ARHGAP15 counteracts this pathway, thereby limiting RAC1-ATG16L1 signaling and autophagy. Thus, our findings identify a mechanism that, in contrast to the Hippo-LATS and PIDDosome-p53 pathways, does not circumvent the effects of centrosome amplification by disabling cell-cycle arrest pathways but activates a corrective mechanism to reduce centrosome number. - Source: PubMed
Publication date: 2026/08/23
Coelho Paula AGlover David M - Messenger RNAs (mRNAs) accumulate at centrosomes in mitosis and interphase, yet the mechanisms governing their localization and their functional significance remain poorly understood. Here, we identify a centriolar satellite - RNA-binding protein (RBP) pathway that regulates CEP350 mRNA localization and stability to support centriole overduplication. We find that CEP350 mRNA localizes to centrosomes in S phase in a microtubule (MT)-dependent manner. The RBP, UNK and centriolar satellite protein, CEP131 stabilize CEP350 mRNA and promote its steady-state levels and centrosomal protein accumulation. CEP350 is required for PLK4-induced centriole overduplication but has limited effects on canonical centriole duplication. Disrupting the centriolar satellite - RBP pathway reduces centriole overduplication in triple-negative breast cancer cells, indicating CEP131 and UNK are potential therapeutic targets for reducing centriole overduplication. - Source: PubMed
Publication date: 2026/08/05
Martinez AbrahamPearson Chad G - Polo-like kinase 4 (PLK4), a master regulator of centrosome duplication, has emerged as an attractive therapeutic target in oncology. Notably, the synthetic lethality between PLK4 inhibition and TRIM37 amplification provides a strong rationale for targeted tumor intervention. However, the limited structural diversity of current PLK4 inhibitors constrains further development. Herein, structure-guided scaffold-hopping and fragment growth strategies were employed to develop a series of structurally novel quinazoline-based PLK4 inhibitors. The optimized compound B33 (ZSL-M028) exhibited potent PLK4 inhibition (IC50 = 1.1 nM), excellent selectivity over Aurora A kinase (over 1600-fold), and favorable ADME and pharmacokinetic properties, including an oral bioavailability of 55.4%. M028 further demonstrated significant in vitro and in vivo antitumor activity against TRIM37-amplified neuroblastoma with a favorable safety profile. Overall, M028 represents a promising lead for PLK4 inhibition, and offers new opportunities for precision therapy in TRIM37-amplified neuroblastoma. - Source: PubMed
Liu NianQi ZehuiSun WenqiangTong MinghuiShi XuanWang HanMu ShuyiHu NingyuanLuo ZiruiFan CunzhengZhang HaoyuGao ZixuanSun YinZhao DongmeiCheng Maosheng