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)
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
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)
Review
Biochemistry & Molecular Biology
Mrunal Jadhav, Kaksha Sankhe, Richie R. Bhandare, Zehra Edis, Samir Haj Bloukh, Tabassum Asif Khan
Summary: Recent decades have seen significant progress in the discovery of anticancer drugs containing pyrimidine structures, which exhibit diverse mechanisms of action, including inhibition of protein kinases. Literature and patent analysis reveal extensive research and application of pyrimidine derivatives in the field of anticancer drugs.
Article
Oncology
Manuela Mancini, Cecilia Monaldi, Sara De Santis, Michela Rondoni, Cristina Papayannidis, Chiara Sartor, Antonio Curti, Samantha Bruno, Michele Cavo, Simona Soverini
Summary: This study aimed to identify new therapeutic targets in the pathogenesis of systemic mastocytosis (SM). The results identified Aurora kinase A and Polo-like kinase 1 as potential targets for SM treatment. Inhibiting these kinases can induce apoptotic cell death in SM cell lines, suggesting it as an attractive therapeutic strategy. Further clinical development of inhibitors for these kinases could improve the outcome of patients with advanced SM.
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
Oncology
Manuela Mancini, Sara De Santis, Cecilia Monaldi, Fausto Castagnetti, Annalisa Lonetti, Samantha Bruno, Elisa Dan, Barbara Sinigaglia, Gianantonio Rosti, Michele Cavo, Gabriele Gugliotta, Simona Soverini
Summary: In this study, a new therapeutic strategy combining Aurora kinase A or PLK1 inhibition with WEE1 inhibition was proposed for the treatment of chronic myeloid leukemia. The combination was found to significantly enhance apoptotic cell death by inducing DNA damage and successive replication cycles.
FRONTIERS IN ONCOLOGY
(2022)
Article
Multidisciplinary Sciences
Ryuzaburo Yuki, Yuki Ikeda, Ryuji Yasutake, Youhei Saito, Yuji Nakayama
Summary: SH2D4A is a newly identified mitotic regulator that promotes centrosome maturation and microtubule formation by inhibiting PP1 phosphatase. It accelerates spindle formation and supports mitotic progression.
SCIENTIFIC REPORTS
(2023)
Article
Multidisciplinary Sciences
Jin-Gyeong Park, Hanul Jeon, Sangchul Shin, Chiman Song, Hyomin Lee, Nak-Kyoon Kim, Eunice EunKyeong Kim, Kwang Yeon Hwang, Bong-Jin Lee, In-Gyun Lee
Summary: This study identified a conserved region of CEP192 that interacts with AURKA and revealed the structural basis for CEP192-mediated regulation of AURKA at the centrosome. This regulation is distinct from TPX2-mediated regulation on the spindle microtubule.
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)
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
Biochemistry & Molecular Biology
Yasuhiro Kurasawa, Kyu Joon Lee, Huiqing Hu, Kieu T. M. Pham, Ziyin Li
Summary: The study demonstrates that TbPLK and TbAUK1 phosphorylate the cytokinesis regulators CIF1 and CIF2 in Trypanosoma brucei. TbPLK interacts with CIF1 in S/G2 phases, maintaining its localization until early mitosis; TbAUK1 maintains CIF1 and CIF2 localization from late mitosis.
Article
Biochemistry & Molecular Biology
Danda Chapagai, George Merhej, Campbell McInnes, Michael D. Wyatt
Summary: Polo-like kinase 1 (PLK1) is a crucial protein kinase involved in multiple mitotic processes, and its regulation is mediated by the interaction between its kinase domain (KD) and phosphopeptide-binding polobox domain (PBD). This study compared the activity of PBD-binding molecules (abbapolins) with KD inhibitors to understand the conformational features of PLK1. Abbapolins were found to thermally stabilize PLK1, while KD inhibitors caused a decrease in soluble PLK1 and a less stable conformation. Binding measurements and cellular consequences also revealed distinct effects of KD versus PBD engagement, suggesting the relief of autoinhibited PLK1 by KD binders. These findings have significant implications for targeting PLK1 and the development of ATP-competitive PLK1 inhibitors.
ACS CHEMICAL BIOLOGY
(2023)
Article
Cell Biology
Yi Zhao, Juan Yang, Jiarui Liu, Yiqing Cai, Yang Han, Shunfeng Hu, Shuai Ren, Xiangxiang Zhou, Xin Wang
Summary: The study reveals that PLK4 is a potential target for DLBCL treatment, with the PLK4 inhibitor CFI-400945 showing efficacy in combination with doxorubicin by activating p53 and Hippo/YAP tumor suppressor signaling pathways as well as DNA damage response to induce anti-tumor effects.
CELL DEATH & DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Manuela La Montagna, Lei Shi, Peter Magee, Sudhakar Sahoo, Matteo Fassan, Michela Garofalo
Summary: AMP-activated protein kinase (AMPK) plays a critical role in non-small cell lung cancer, with loss of AMPKα potentially promoting KRAS-mediated lung tumorigenesis. Additionally, AMPKα might regulate LDHB activation through modulation of lncRNA KIMAT1. These findings offer a new axis for therapeutic research.
CELL DEATH AND DIFFERENTIATION
(2021)
Article
Cell Biology
Hiroka Kashihara, Shuhei Chiba, Shin-ichiro Kanno, Koya Suzuki, Tomoki Yano, Sachiko Tsukita
Article
Cell Biology
Izumi Dateyama, Yoshihiro Sugihara, Shuhei Chiba, Reo Ota, Risa Nakagawa, Tetsuo Kobayashi, Hiroshi Itoh
JOURNAL OF CELL SCIENCE
(2019)
Article
Cell Biology
Sachiko Fujiwara, Tsubasa S. Matsui, Kazumasa Ohashi, Kensaku Mizuno, Shinji Deguchi
Editorial Material
Biochemistry & Molecular Biology
Siew Cheng Phua, Shuhei Chiba, Masako Suzuki, Emily Su, Elle C. Roberson, Ganesh V. Pusapati, Stephane Schurmans, Mitsutoshi Setou, Rajat Rohatgi, Jeremy F. Reiter, Koji Ikegami, Takanari Inoue
Article
Evolutionary Biology
Daiki X. Sato, Yuu Ishii, Tomoaki Nagai, Kazumasa Ohashi, Masakado Kawata
BMC EVOLUTIONARY BIOLOGY
(2019)
Article
Cell Biology
Yusuke Isozaki, Kouki Sakai, Kenta Kohiro, Katsuhiko Kagoshima, Yuma Iwamura, Hironori Sato, Daniel Rindner, Sachiko Fujiwara, Kazunari Yamashita, Kensaku Mizuno, Kazumasa Ohashi
MOLECULAR BIOLOGY OF THE CELL
(2020)
Article
Engineering, Biomedical
Luqman Khan, Katsumi Sato, Shinichi Okuyama, Takeshi Kobayashi, Kazumasa Ohashi, Katsuya Hirasaka, Takeshi Nikawa, Kunio Takada, Atsushi Higashitani, Kenji Abiko
JOURNAL OF THE MECHANICAL BEHAVIOR OF BIOMEDICAL MATERIALS
(2020)
Article
Cell Biology
Yohei Katoh, Shuhei Chiba, Kazuhisa Nakayama
MOLECULAR BIOLOGY OF THE CELL
(2020)
Article
Cell Biology
Misato Okazaki, Takuya Kobayashi, Shuhei Chiba, Ryota Takei, Luxiaoxue Liang, Kazuhisa Nakayama, Yohei Katoh
MOLECULAR BIOLOGY OF THE CELL
(2020)
Article
Cell Biology
Komaki Ninomiya, Kai Ohta, Kazunari Yamashita, Kensaku Mizuno, Kazumasa Ohashi
Summary: PLEKHG4B plays a crucial role in epithelial cell-cell junction formation by regulating actin remodeling and modulating the activities of Cdc42 and RhoA. Knockdown of PLEKHG4B leads to open junctions and aberrant myosin activity.
JOURNAL OF CELL SCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Yamato Ishida, Takuya Kobayashi, Shuhei Chiba, Yohei Katoh, Kazuhisa Nakayama
Summary: Compound heterozygous mutations in IFT144 gene can lead to severe ciliary defects through a complex mechanism, where one allele can cause severe ciliary defects when combined with a hypomorphic allele.
HUMAN MOLECULAR GENETICS
(2021)
Article
Biology
Sayaka Fujisawa, Hantian Qiu, Shohei Nozaki, Shuhei Chiba, Yohei Katoh, Kazuhisa Nakayama
Summary: INPP5E is localized on the ciliary membrane via its prenyl moiety, with the ARL3 and ARL13B GTPases contributing to maintaining this localization through different mechanisms, with ARL13B mainly determining the ciliary localization of INPP5E through direct binding to it.
Article
Cell Biology
Shunya Hiyamizu, Hantian Qiu, Laura Vuolo, Nicola L. Stevenson, Caroline Shak, Kate J. Heesom, Yuki Hamada, Yuta Tsurumi, Shuhei Chiba, Yohei Katoh, David J. Stephens, Kazuhisa Nakayama
Summary: The dynein-2 complex is transported anterogradely within cilia to drive retrograde trafficking of the intraflagellar transport (IFT) machinery containing IFT-A and IFT-B complexes. There are multiple interactions between the dynein-2 and IFT-B subunits, including WDR60 and the DYNC2H1-DYNC2LI1 dimer from dynein-2, and IFT54 and IFT57 from IFT-B. These interactions play a crucial role in the connection between dynein-2 and IFT-B.
JOURNAL OF CELL SCIENCE
(2023)
Article
Multidisciplinary Sciences
Mingyue Jin, Sakiko Matsumoto, Takashi Ayaki, Hodaka Yamakado, Tomoyuki Taguchi, Natsuko Togawa, Ayumu Konno, Hirokazu Hirai, Hiroshi Nakajima, Shoji Komai, Ryuichi Ishida, Syuhei Chiba, Ryosuke Takahashi, Toshifumi Takao, Shinji Hirotsune
Summary: Parkinson's disease is a progressive neurodegenerative disorder, and research suggests that tyrosine hydroxylase can facilitate the formation of oligomers of alpha-synuclein through dopamine modification, potentially impacting disease pathogenesis and degeneration of dopaminergic neurons.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Koya Suzuki, Kosuke Yamaga, Reitaro Tokumasu, Tatsuya Katsuno, Hiroo Tanaka, Shuhei Chiba, Takeshi Yagi, Ichiro Katayama, Atsushi Tamura, Hiroyuki Murota, Sachiko Tsukita
Summary: Hair retention in infant mice is regulated by Claudin (CLDN)-1 and CLDN3, which maintain the appropriate layered architecture of hair follicles. Deficiencies in these proteins can lead to hair loss.
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
(2023)
