Article
Chemistry, Medicinal
Jifa Zhang, Lele Zhang, Jiaxing Wang, Liang Ouyang, Yuxi Wang
Summary: PLK1 plays an important role in cellular functions and is associated with cancer prognosis and cell proliferation. Although several inhibitors have entered clinical trials, their poor specificity has hindered their development. Recent research has discovered PLK1 inhibitors with higher selectivity and improved characteristics. This review emphasizes the structure-activity relationships of these inhibitors, providing insights for the development of antitumor drugs.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
SeongShick Ryu, Jung-Eun Park, Young Jin Ham, Daniel C. Lim, Nicholas P. Kwiatkowski, Do-Hee Kim, Debabrata Bhunia, Nam Doo Kim, Michael B. Yaffe, Woolim Son, Namkyoung Kim, Tae-Ik Choi, Puspanjali Swain, Cheol-Hee Kim, Jin-Young Lee, Nathanael S. Gray, Kyung S. Lee, Taebo Sim
Summary: This study successfully designed and synthesized a series of macrocyclic peptidomimetics with high selectivity and inhibitory activities against Plk1's PBD. Compound 16e showed more potent inhibitory activity than the previous PMQSpTPL. The pi-π stacking interaction between 16a and Arg516 revealed a new design strategy, and PEGylation of 16h caused delocalization and mitotic failure of Plk1. Furthermore, the number of phospho-H3-positive cells in zebrafish embryos correlated with the amount of 16a. These findings suggest that macrocyclic peptidomimetics can serve as valuable templates for potent and novel Plk1-PBD inhibitors.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Immunology
Zhenqiang Gao, Cuiting Zheng, Yaqi Xing, Xiyu Zhang, Yunfei Bai, Chen Chen, Yuanyuan Zheng, Wen Wang, Hongbing Zhang, Yan Meng
Summary: In sepsis, Plk-1 promotes the development of SIMD. Inhibition of Plk-1 improves LPS-induced myocardial injury and inflammation, and enhances the survival rate of mice. Plk-1 inhibition also impedes NF-κB signal pathway activation.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Review
Pharmacology & Pharmacy
Styliani Iliaki, Rudi Beyaert, Inna S. Afonina
Summary: PLK1 is a Ser/Thr kinase that plays crucial roles in cell cycle regulation, DNA damage response, apoptosis, and cancer progression. Overexpression of PLK1 is associated with poor prognosis in cancer, making it an attractive therapeutic target.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Respiratory System
Rongrong Chen, Hongfei Wang, Cuiting Zheng, Xiyu Zhang, Li Li, Shengwei Wang, Hongyu Chen, Jing Duan, Xian Zhou, Haiyong Peng, Jing Guo, Anchen Zhang, Feifei Li, Wang Wang, Yu Zhang, Jun Wang, Chen Wang, Yan Meng, Xinling Du, Hongbing Zhang
Summary: The study aimed to investigate the role of the mitotic regulator Polo-like kinase 1 (PLK1) in the development of pulmonary hypertension (PH). The results showed that hypoxia stimulated the expression of PLK1 through the induction of HIF1a and RELA. Overexpression of PLK1 was essential for the development of PH, suggesting that PLK1 could be a potential druggable target for PH.
RESPIRATORY RESEARCH
(2023)
Article
Cell Biology
Midori Ohta, Zhiling Zhao, Di Wu, Shaohe Wang, Jennifer L. Harrison, J. Sebastian Gomez-Cavazos, Arshad Desai, Karen F. Oegema
Summary: PLK1 not only controls the expansion of PCM, but also independently regulates the generation of binding sites for gamma-tubulin complexes on the PCM matrix. Inhibiting PLK1-dependent gamma-tubulin docking sites leads to spindle defects and impaired chromosome segregation, highlighting the importance of phospho-regulated centrosomal gamma-tubulin docking sites in spindle assembly.
JOURNAL OF CELL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Juyoung Kim, Gohta Goshima
Summary: Mitosis is a fundamental process in eukaryotes, and its essential genes can be bypassed through genetic or environmental changes. This study discovered the bypass of essentiality of a mitosis regulator, Polo-like kinase, through specific mutations and down-regulation of glucose uptake. The study also identified casein kinase I as an alternative mechanism for microtubule nucleation. The findings have implications for understanding mitosis and selecting chemotherapeutic compounds.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Sylvia Nkombo Nkoula, Griselda Velez-Aguilera, Batool Ossareh-Nazari, Lucie Van Hove, Cristina Ayuso, Veronique Legros, Guillaume Chevreux, Laura Thomas, Geraldine Seydoux, Peter Askjaer, Lionel Pintard
Summary: This study reveals that nuclear pore complex (NPC) disassembly is a stepwise process involving both Polo-like kinase 1 (PLK-1)-dependent and -independent steps. PLK-1 targets multiple NPC subcomplexes by phosphorylating intrinsically disordered regions (IDRs) of multivalent linker nucleoporins. The targeting of IDRs of multivalent linker nucleoporins is an evolutionarily conserved driver of NPC disassembly during mitosis.
Article
Biochemical Research Methods
Rand Shahin, Nabil N. Al-Hashimi, Nour el-Huda Daoud, Salah Aljamal, Omar Shaheen
Summary: Targeting Polo-like kinase 1 (Plk1) using molecular inhibitors is a promising approach for tumor therapy. This study successfully identified a new QSAR model and pharmacophores for Plk1 inhibition, which were used to screen and validate new Plk1 inhibitory hits from a database.
JOURNAL OF MOLECULAR GRAPHICS & MODELLING
(2021)
Article
Biochemistry & Molecular Biology
Yingbing Zhang, Ying Yang, Peipei Qiao, Xiyue Wang, Ruiluan Yu, Hongzheng Sun, Xupeng Xing, Yong Zhang, Jianmin Su
Summary: This study demonstrates the significant roles of CHAF1b in preimplantation embryos, possibly through regulating epigenetic modifications and lineage specification.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Review
Oncology
Chuanyong Zhang, Chuangye Ni, Hao Lu
Summary: PLK2 plays an important role in the cell cycle, cell differentiation, and maintaining neural homeostasis. Dysfunction of PLK2 can lead to cell cycle disorders and developmental retardation. Additionally, PLK2 may promote cell survival or apoptosis in response to stress stimuli. However, research on the role of PLK2 in immunity to viral infection is limited compared to other family members.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Oksana Goroshchuk, Iryna Kolosenko, Elena Kunold, Linda Vidarsdottir, Mohammad Pirmoradian, Alireza Azimi, Rozbeh Jafari, Caroline Palm-Apergi
Summary: PLK1 is an important cell cycle kinase and the side effects of the anticancer drug volasertib may be due to lack of specificity, highlighting the importance of identifying its potential off-targets for future clinical trials and drug development. This study utilized TPP to identify protein-wide targets of volasertib and found that phosphatidylinositol phosphate and prostaglandin metabolism pathways are affected by volasertib.
Article
Biochemistry & Molecular Biology
Femi Olawale, Opeyemi Iwaloye, Olusola Olalekan Elekofehinti
Summary: The over-expression of PLK1 is linked to cancer prognosis, and this study identified potential inhibitors by targeting the NCD and PBD domains of PLK1 through pharmacophore modeling and molecular docking. The hit compounds showed promising inhibitory activity and drug-like properties for further experimental validation.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Biochemistry & Molecular Biology
Sheng Yan, Bin Peng, Shifeng Kan, Guangcan Shao, Zhikai Xiahou, Xiangyan Tang, Yong-Xiang Chen, Meng-Qiu Dong, Xiao Liu, Xingzhi Xu, Jing Li
Summary: This article investigates the impact of O-GlcNAc transferase (OGT) on PLK1, and finds that OGT can modify PLK1 through O-GlcNAcylation. Further research reveals that the T291A and T291N mutations increase the stability of PLK1 and lead to chromosome segregation defects and uterine carcinoma. The findings suggest that OGT exerts its mitotic function partially through O-GlcNAcylation of PLK1, which may contribute to tumorigenesis by elevating O-GlcNAc levels.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Review
Pharmacology & Pharmacy
Ilma Shakeel, Neha Basheer, Gulam Mustafa Hasan, Mohammad Afzal, Md. Imtaiyaz Hassan
Summary: PLK1, a conserved mitotic serine-threonine protein kinase, plays important roles in cell division and genome stability. Its expression is controlled by cell cycle stages and blocking PLK1 expression can inhibit tumor cell proliferation and induce apoptosis, making it an attractive target for drug development.
JOURNAL OF DRUG TARGETING
(2021)
Review
Cell Biology
Lucie Tumova, Michal Zigo, Peter Sutovsky, Marketa Sedmikova, Pavla Postlerova
Summary: The interaction between sperm and the zona pellucida (ZP) is crucial for successful fertilization in mammals, involving the binding of sperm surface ligands to complementary carbohydrates of ZP. Understanding the mechanisms of sperm-ZP interaction is critical for diagnosing infertility and improving assisted reproductive therapies/technologies.
Article
Developmental Biology
Momal Sharif, Karl Kerns, Peter Sutovsky, Nicolai Bovin, David J. Miller
Summary: Studies have shown that progesterone-induced sperm release requires active CatSper channels and proteasomal degradation, indicating that hyperactivation and proteolysis are vital parts of the mechanism for sperm movement.
Article
Biochemistry & Molecular Biology
Lauren E. Hamilton, Morgan Lion, Luis Aguila, Joao Suzuki, Genevieve Acteau, Nicole Protopapas, Wei Xu, Peter Sutovsky, Mark Baker, Richard Oko
Summary: This study discovered the presence of core histones in the perinuclear theca (PT) of eutherian sperm, which are newly synthesized during spermiogenesis and play a role in chromatin remodeling of the male pronucleus post-fertilization. These histones are localized in specific sub-compartments of the PT and contribute to early embryonic development, highlighting their functional significance in reproductive processes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Vladimir Baran, Jozef Pisko
Summary: The preimplantation period of embryogenesis plays a crucial role in mammalian development, and cellular abnormalities during this period are the main cause of fetal developmental disorders. Research has found that DNA damage induced before DNA synthesis can significantly affect the preimplantation development of the embryo, and the extent of DNA damage is related to this developmental ability. Although one-cell embryos can correct the first cleavage cycle, a segregation disorder of condensed chromatin after the first cleavage can result in the formation of micronuclei.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Agriculture, Dairy & Animal Science
Mohammed S. Liman, Abubeker Hassen, Lyndy J. McGaw, Peter Sutovsky, Dietmar E. Holm
Summary: This review examined the impact of semen cryopreservation and tannins on sperm function, highlighting the role of tannins in combating reactive oxygen species and promoting successful fertilization. Additionally, the effects of tannin extract feed supplementation on male fertility were investigated, and the potential benefits of tannins as additives in semen extenders were explored.
Article
Biology
Michal Zigo, Karl Kerns, Sidharth Sen, Clement Essien, Richard Oko, Dong Xu, Peter Sutovsky
Summary: Zinc-interacting proteins in porcine sperm undergo changes during sperm maturation, particularly during sperm capacitation. These changes may be associated with Huntington's and Parkinson's disease pathways. The findings have implications for reproductive health, assisted reproductive therapy, and livestock breeding.
COMMUNICATIONS BIOLOGY
(2022)
Article
Reproductive Biology
Alexandra Spirkova, Veronika Kovarikova, Zuzana Sefcikova, Jozef Pisko, Martina Ksinanova, Juraj Koppel, Dusan Fabian, Stefan Cikos
Summary: The study reveals that glutamic acid can affect preimplantation embryo development through cell membrane receptors. High extracellular concentrations of glutamic acid can inhibit blastocyst development, which is of practical significance.
BIOLOGY OF REPRODUCTION
(2022)
Review
Biochemistry & Molecular Biology
Meghan Lawlor, Michal Zigo, Karl Kerns, In Ki Cho, Charles A. Easley, Peter Sutovsky
Summary: Huntington's Disease is a fatal neurodegenerative disease with motor dysfunction and cognitive deficits. It also leads to reduced fertility. Although there are pharmaceuticals to manage its symptoms, an effective treatment for the disease is yet to be approved. Identification of genes, diagnostic biomarkers, and therapeutic target pathways could help in early diagnosis and management of the disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Vladimir Baran, Alexandra Mayer
Summary: After fertilization, the remodeling of the oocyte and sperm genome is crucial for the successful initiation of mitotic activity in the fertilized oocyte and subsequent proliferation of the early embryo. The specific nature of gene totipotency in early cleavage embryos leads to differences in cell cycle control mechanisms compared to somatic cells. This review focuses on the Chk1 kinase as an important factor in monitoring DNA integrity during early embryogenesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Michal Zigo, Karl Kerns, Peter Sutovsky
Summary: The present study focused on the role of the ubiquitin-proteasome system (UPS) in sperm capacitation. High-resolution, quantitative LC-MS analysis revealed differentially expressed proteins associated with sperm capacitation, hyperactivation, metabolism, acrosomal exocytosis, and fertilization. Further investigation confirmed the involvement of specific proteins, such as CSE1L, PFDN4, and STK39, in sperm capacitation. This research provides insights into potential pharmacological mechanisms to modulate sperm fertilizing ability in animals and humans.
Article
Cell Biology
J. T. Soley, L. du Plessis, M. Sutovsky, P. Sutovsky
Summary: This paper provides the first detailed description of the spermiogenesis process in ostriches and one of the few in any avian species. The steps of spermiogenesis were observed and illustrated using light microscopy and supplemented with ultrastructural observations, PNA labeling, and immunocytochemical labeling. Eight steps were identified, showing similarities with non-passerine birds. However, fewer steps were observed during the development of round spermatids compared to other bird species. This research has implications for comparative reproduction, animal science, and evolutionary biology.
CELL AND TISSUE RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Lucie Knoblochova, Tomas Duricek, Michaela Vaskovicova, Chrysoula Zorzompokou, Diana Rayova, Ivana Ferencova, Vladimir Baran, Richard M. Schultz, Eva R. Hoffmann, David Drutovic
Summary: Checkpoint kinase CHK1 regulates cell cycle progression in early mouse embryos by restraining CDK1 kinase activity through CDC25A phosphatase degradation. It also ensures the long G2 phase needed for genome activation and reprogramming gene expression in two-cell stage mouse embryos. Depletion of CHK1 leads to DNA damage and chromosome segregation errors, resulting in aneuploidy and infertility.
Article
Biology
Dalen Zuidema, Alexis Jones, Won-Hee Song, Michal Zigo, Peter Sutovsky
Summary: The degradation of sperm-borne mitochondria after fertilization, known as post-fertilization sperm mitophagy, ensures exclusive maternal inheritance of mitochondrial DNA. This process involves the ubiquitin-proteasome system and other autophagic cofactors. The study used mass spectrometry and a porcine cell-free system to identify proteins involved in post-fertilization sperm mitophagy. The findings confirm the involvement of known determinants and provide a list of candidate cofactors for future studies.
Article
Obstetrics & Gynecology
Veronika Kovarikova, Alexandra Spirkova, Zuzana Sefcikova, Jozef Pisko, Laura Kalatova, Juraj Koppel, Dusan Fabian, Stefan Cikos
Summary: This study found that the activation of GABA receptors by certain substances can have negative effects on preimplantation embryos. The presence of various GABA receptor subunits was detected in mouse blastocysts and ovulated oocytes. Adding GABA or specific GABA receptor agonists to the culture medium significantly increased cell death in blastocysts, and this effect was prevented by GABA receptor antagonists.
REPRODUCTIVE MEDICINE AND BIOLOGY
(2023)
Review
Andrology
George Anifandis, Helen G. Tempest, Rafael Oliva, Grace M. Swanson, Mara Simopoulou, Charles A. Easley, Michael Primig, Christina Messini, Paul J. Turek, Peter Sutovsky, Steve J. Ory, Stephen A. Krawetz
Summary: The COVID-19 pandemic has caused a global health emergency, impacting 188 countries. The unique features of rapid spread and high mortality rate have led to an unprecedented global health crisis. The virus primarily affects the lungs but can also target other vital organs, with potential impacts on reproductive organs still unclear. The halt in reproductive services has highlighted the importance of diagnostic tests and research in supporting public health policies.
SYSTEMS BIOLOGY IN REPRODUCTIVE MEDICINE
(2021)