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
- ∼50% of fertilized eggs arrest during human pre-implantation development, representing a major bottleneck for assisted reproductive technology. The underlying causes remain controversial. By imaging ∼150 live human and monkey fertilized eggs for up to 5 days, we uncovered that the second mitotic divisions are the most error-prone, accounting for early embryonic arrest. Stochastic centriole overduplication, which could be effectively suppressed by transient treatment with PLK4 inhibitor centrinone, predisposed 2-cell blastomeres to assembling multipolar spindles and missegregating chromosomes. Missegregated chromosomes in turn resulted in the formation of most micronuclei in human embryos and led to the arrest or death of daughter blastomeres. By contrast, late embryonic arrest was largely independent of chromosome missegregations but involved the activation of endoplasmic reticulum stress response, which could impair the expression of subsets of junctional and cell polarity proteins required for blastocyst formation. Thus, two distinct causes contribute to the low efficiency of human pre-implantation development. - Source: PubMed
Publication date: 2026/06/11
Li ZixuanLeng LizhiZhai JingleiWang XiaowenYang WulingWang ShuhuiWan HaifengZhang ShuopingGong FeiLiao XiLi YuhuiZeng QingChen YansuXiang ZhenyuLiu FeiyaoHe FuchuYang YunWang HongmeiXu XiaomingLin GeSo Chun - Polo-like kinase 4 (PLK4) is a serine/threonine-protein kinase that plays a pivotal role in centriole biogenesis and, as such, represents a master regulator of centriole duplication. Due to its importance in cancer development and progression, PLK4 represents an attractive target for the development of novel therapeutics. Herein, we present a series of molecular degraders of PLK4, based on the highly selective PLK4 inhibitor centrinone, with the aim of targeting PLK4 for degradation the ubiquitin-proteasome system. While all synthesized degraders retained low nanomolar binding affinities to the kinase domain of PLK4, large differences were found with respect to their ability to change cellular PLK4 levels. We uncover a complex pharmacological profile of the most potent degraders, D6 and D10, consisting of concomitant lowering of PLK4 levels through degradation, and enhancing PLK4 levels through inhibition of its autoregulation - dependent on its localization at the centrioles. - Source: PubMed
Publication date: 2026/05/29
Kovacevic AndrejSalim AleksandarBorges CrisálidaMeraldi PatrickHoogendoorn Sascha - Gasdermins have been traditionally recognized for their canonical pore-forming activity in pyroptosis and generally considered as a tumor suppressor due to their low endogenous expression in various types of cancers. However, the pyroptosis-independent role of gasdermins in cellular biological processes remains poorly understood, sparking debates on their actual contribution to cancer pathogenesis. Here, we demonstrate a novel facet of GSDME as an epigenetic modifier that promotes melanoma development through the regulation of the centriole biogenesis regulator PLK4. Unexpectedly, GSDME expression is significantly up-regulated in melanoma, induced by prominent hypo-methylation at its promoter. The deficiency of GSDME prominently suppresses tumor growth and metastasis of melanoma, independent of CD8+ T cell-dependent anti-tumor immunity. Mechanistically, GSDME forms a complex with SMARCA5 and NCL in the nucleus, functioning as an epigenetic regulator, particularly facilitating the transcription of centriole biogenesis regulator PLK4 by increasing its promoter chromatin accessibility. The regulation of PLK4 is greatly implicated in the oncogenic role of GSDME in melanoma. Ultimately, this GSDME-SMARCA5/NCL-PLK4 axis is validated in patients with melanoma and has been proved of promising prognostic potential. Altogether, these results demonstrate that GSDME could be a critical oncogene through its pyroptosis-independent epigenetic regulatory function. - Source: PubMed
Publication date: 2026/05/25
Du JuanYang YuqiZhao MaoZhang HengxiangLi XiaQu DiWang JianzhangWang XiangxuYi XiuliMa JingjingWang HuinaWang HaoShi QiongTian YangziZhang BaoluGuo SenGao TianwenGuo WeinanLi Chunying - Centrosomes are key microtubule-organizing centers required for accurate spindle assembly and chromosome segregation, and their dysfunction in cancer creates therapeutic vulnerabilities. Prior work identified a synthetic lethal interaction between TRIM37 overexpression and Polo-like kinase 4 inhibition (PLK4i) in 17q23-amplified tumors, motivating the clinical development of centrosome-depleting PLK4 inhibitors. However, the broader determinants of sensitivity and resistance to PLK4 inhibition remain poorly defined. Using genome-wide CRISPR-Cas9 screening, we identify multiple genetic suppressors of sensitivity to centrosome depletion, including loss of as a general escape mechanism, mediated by enhanced activation of Aurora kinase A (AURKA) on the spindle. This process requires NuMA, which scaffolds robust acentrosomal spindle assembly, and operates independently of the TRIM37-regulated pathway that restores pericentriolar material (PCM) foci to reconstitute microtubule-organizing center activity. We further show that centrosome depletion creates a dependence on the AURKA-TPX2 axis for spindle assembly, such that modulation of this pathway shapes cellular responses to PLK4 inhibition. Loss of PPP6C elevates AURKA activity and confers resistance, whereas disruption of the AURKA-TPX2 axis sensitizes cells to centrosome depletion. Together, these findings reveal how centrosome depletion rewires mitotic organization, rendering cells dependent on distinct adaptive spindle assembly pathways. - Source: PubMed
Publication date: 2026/05/06
Yeow Zhong YChang Fang-ChiXu Lance YHolland Andrew J - Human aneuploid conception, a leading cause of infertility, pregnancy loss, and congenital disorders (e.g. Down's syndrome), arises from errors in chromosome segregation during oocyte meiosis or embryonic mitosis. While advanced maternal age is a well-established risk factor, significant inter-individual variation exists among younger women, suggesting a substantial role for maternal genetic determinants. - Source: PubMed
Publication date: 2026/05/13
Ha SiyaoLiu WenyiYuan PingYuan ShangyaCao ChunweiMeng AnmingChen Hui