keyword
https://read.qxmd.com/read/38456968/building-the-centrosome-plk-1-controls-multimerization-of-spd-5
#1
JOURNAL ARTICLE
Paul Conduit
Centrosome maturation relies on the assembly of an underlying molecular scaffold. In this issue of JCB, Rios et al. (https://doi.org/10.1083/jcb.202306142) use cross-linking mass spectrometry to reveal how PLK-1 phosphorylation promotes intermolecular SPD-5 self-association that is essential for scaffold formation.
April 1, 2024: Journal of Cell Biology
https://read.qxmd.com/read/38456967/multivalent-coiled-coil-interactions-enable-full-scale-centrosome-assembly-and-strength
#2
JOURNAL ARTICLE
Manolo U Rios, Małgorzata A Bagnucka, Bryan D Ryder, Beatriz Ferreira Gomes, Nicole E Familiari, Kan Yaguchi, Matthew Amato, Weronika E Stachera, Łukasz A Joachimiak, Jeffrey B Woodruff
The outermost layer of centrosomes, called pericentriolar material (PCM), organizes microtubules for mitotic spindle assembly. The molecular interactions that enable PCM to assemble and resist external forces are poorly understood. Here, we use crosslinking mass spectrometry (XL-MS) to analyze PLK-1-potentiated multimerization of SPD-5, the main PCM scaffold protein in C. elegans. In the unassembled state, SPD-5 exhibits numerous intramolecular crosslinks that are eliminated after phosphorylation by PLK-1. Thus, phosphorylation induces a structural opening of SPD-5 that primes it for assembly...
April 1, 2024: Journal of Cell Biology
https://read.qxmd.com/read/38454090/neuropathological-stage-dependent-proteome-mapping-of-the-olfactory-tract-in-alzheimer-s-disease-from-early-olfactory-related-omics-signatures-to-computational-repurposing-of-drug-candidates
#3
JOURNAL ARTICLE
Paz Cartas-Cejudo, Adriana Cortés, Mercedes Lachén-Montes, Elena Anaya-Cubero, Elena Puerta, Maite Solas, Joaquín Fernández-Irigoyen, Enrique Santamaría
Alzheimer's disease (AD) is the most common form of dementia, characterized by an early olfactory dysfunction, progressive memory loss, and behavioral deterioration. Albeit substantial progress has been made in characterizing AD-associated molecular and cellular events, there is an unmet clinical need for new therapies. In this study, olfactory tract proteotyping performed in controls and AD subjects (n = 17/group) showed a Braak stage-dependent proteostatic impairment accompanied by the progressive modulation of amyloid precursor protein and tau functional interactomes...
March 7, 2024: Brain Pathology
https://read.qxmd.com/read/38272206/accelerated-aging-and-microsatellite-instability-in-recessive-dystrophic-epidermolysis-bullosa-associated-cutaneous-squamous-cell-carcinoma
#4
JOURNAL ARTICLE
Catherine A A Lee, Siyuan Wu, Yuen Ting Chow, Eric Kofman, Valencia Williams, Megan Riddle, Cindy Eide, Christen L Ebens, Markus H Frank, Jakub Tolar, Kristen P Hook, Saud H AlDubayan, Natasha Y Frank
Recessive dystrophic epidermolysis bullosa (RDEB) is a severely debilitating disorder caused by mutations in COL7A1 and is characterized by extreme skin fragility, chronic inflammation and fibrosis. A majority of RDEB patients develop squamous cell carcinoma (SCC), a highly aggressive skin cancer with limited treatment options currently available. In this study, we utilized an approach leveraging WGS and RNA-seq across three different tissues in a single RDEB patient to gain insight into possible mechanisms of RDEB-associated SCC progression and to identify potential therapeutic options...
January 23, 2024: Journal of Investigative Dermatology
https://read.qxmd.com/read/38095634/single-cell-dissection-reveals-the-role-of-aggrephagy-patterns-in-tumor-microenvironment-components-aiding-predicting-prognosis-and-immunotherapy-on-lung-adenocarcinoma
#5
JOURNAL ARTICLE
Xinti Sun, Fei Meng, Minyu Nong, Hao Fang, Chenglu Lu, Yan Wang, Peng Zhang
BACKGROUND: Lung adenocarcinoma (LUAD) is one of the leading malignant cancers. Aggrephagy plays a critical role in key genetic events for various cancers; yet, how aggrephagy functions within the tumor microenvironment (TME) in LUAD remains to be elucidated. METHODS: In this study, by sequential non-negative matrix factorization (NMF) algorithm, pseudotime analysis, cell-cell interaction analysis, and SCENIC analysis, we have shown that aggrephagy genes demonstrated various patterns among different cell types in LUAD TME...
December 13, 2023: Aging
https://read.qxmd.com/read/38072417/methylation-of-plk-1-potentially-drives-bendamustine-resistance-in-leukemia-cells
#6
JOURNAL ARTICLE
Toshikazu Itabashi, Takahiro Ueda, Ryohei Fukunaga, Takeshi Asano, Yasuhiko Itoh
BACKGROUND: Drug resistance remains a significant impediment in leukemia treatment. While Bendamustine hydrochloride (BH) stands out as a promising therapeutic agent for non-Hodgkin' s lymphoma and mantle cell lymphoma, the mechanisms of resistance to BH are not yet fully understood. Our study focuses on elucidating the mechanisms behind bendamustine resistance in leukemia cells, with a specific emphasis on epigenetics. METHODS: Bendamustine-resistant cells were cultivated from human B cell lymphoblastic leukemia cell lines through systematic and sustained exposure to bendamustine, using the limiting dilution method...
December 8, 2023: Journal of Nippon Medical School
https://read.qxmd.com/read/38039555/confinement-in-dual-chain-locked-dna-origami-nanocages-programs-marker-responsive-delivery-of-crispr-cas9-ribonucleoproteins
#7
JOURNAL ARTICLE
Ziqi Xu, Yuxiang Dong, Ningning Ma, Xurong Zhu, Xue Zhang, Hao Yin, Shiqing Chen, Jun-Jie Zhu, Ye Tian, Qianhao Min
Delivery of CRISPR/Cas9 ribonucleoproteins (RNPs) offers a powerful tool for therapeutic genome editing. However, precise manipulation of CRISPR/Cas9 RNPs to switch the machinery on and off according to diverse disease microenvironments remains challenging. Here, we present dual-chain-locked DNA origami nanocages (DL-DONCs) that can confine Cas9 RNPs in the inner cavity for efficient cargo delivery and dual-marker-responsive genome editing in the specified pathological states. By engineering of ATP or miRNA-21-responsive dsDNAs as chain locks on the DONCs, the permeability of nanocages and accessibility of encapsulated Cas9 RNPs can be finely regulated...
December 1, 2023: Journal of the American Chemical Society
https://read.qxmd.com/read/38031763/mechanism-of-co-operation-of-mutant-il-7r-%C3%AE-and-mutant-nras-in-acute-lymphoblastic-leukemia-role-of-myc
#8
JOURNAL ARTICLE
Hila Winer, Wenqing Li, Gisele Rodrigues, Tim Gower, Thomas Joshua Meyer, Julie Hixon, Scott K Durum
Acute lymphoblastic leukemia (ALL) is an aggressive leukemia which can be derived from either T-cell or B-cell precursors. With current treatments, the survival rate is high, but the treatments are highly toxic with severe side effects. Individual mutations in IL7Rssand RAS pathways have been previously shown to be prevalent in ALL and especially in relapsed patients. The relationship of IL-7R77and RAS was investigated by transducing immature mouse thymocytes with the combination of these mutants. The resultant ALL cells were analyzed to identify the regulators and the oncoproteins that are upregulated or downregulated by the combination of IL7Rα with NRAS...
November 30, 2023: Haematologica
https://read.qxmd.com/read/38001717/potential-tumor-suppressor-role-of-polo-like-kinase-5-in-cancer
#9
JOURNAL ARTICLE
Shengqin Su, Mary Ann Ndiaye, Glorimar Guzmán-Pérez, Rebecca Michael Baus, Wei Huang, Manish Suresh Patankar, Nihal Ahmad
The polo-like kinase (PLK) family of serine/threonine kinases contains five members (PLK1-5). Most PLKs are involved in cell cycle regulation and DNA damage response. However, PLK5 is different as it lacks a functional kinase domain and is not involved in cell cycle control. PLK5 remains the least-studied family member, and its role in oncogenesis remains enigmatic. Here, we identified tissues with high PLK5 expression by leveraging the Protein Atlas and GTEx databases with relevant literature and selected ovarian, lung, testis, endometrium, cervix, and fallopian tube tissues as candidates for further investigation...
November 17, 2023: Cancers
https://read.qxmd.com/read/37995185/pp2a-b55-sur-6-promotes-nuclear-envelope-breakdown-in-c-%C3%A2-elegans-embryos
#10
JOURNAL ARTICLE
Sukriti Kapoor, Kuheli Adhikary, Sachin Kotak
Nuclear envelope (NE) disassembly during mitosis is critical to ensure faithful segregation of the genetic material. NE disassembly is a phosphorylation-dependent process wherein mitotic kinases hyper-phosphorylate lamina and nucleoporins to initiate nuclear envelope breakdown (NEBD). In this study, we uncover an unexpected role of the PP2A phosphatase B55SUR-6 in NEBD during the first embryonic division of Caenorhabditis elegans embryo. B55SUR-6 depletion delays NE permeabilization and stabilizes lamina and nucleoporins...
November 22, 2023: Cell Reports
https://read.qxmd.com/read/37879229/polo-like-kinase-1-promotes-sepsis-induced-myocardial-dysfunction
#11
JOURNAL ARTICLE
Zhenqiang Gao, Cuiting Zheng, Yaqi Xing, Xiyu Zhang, Yunfei Bai, Chen Chen, Yuanyuan Zheng, Wen Wang, Hongbing Zhang, Yan Meng
Sepsis-induced myocardial dysfunction (SIMD) is the main cause of mortality in sepsis. In this study, we identified Polo-like kinase 1 (Plk-1) is a promoter of SIMD. Plk-1 expression was increased in lipopolysaccharide (LPS)-treated mouse hearts and neonatal rat cardiomyocytes (NRCMs). Inhibition of Plk-1 either by heterozygous deletion of Plk-1 or Plk-1 inhibitor BI 6727 alleviated LPS-induced myocardial injury, inflammation, cardiac dysfunction, and thereby improved the survival of LPS-treated mice. Plk-1 was identified as a kinase of inhibitor of kappa B kinase alpha (IKKα)...
October 23, 2023: International Immunopharmacology
https://read.qxmd.com/read/37874309/plk3-facilitates-replication-of-swine-influenza-virus-by-phosphorylating-viral-np-protein
#12
JOURNAL ARTICLE
Caiyue Ren, Tong Chen, Shishuo Zhang, Qingxia Gao, Jiahui Zou, Peng Li, Biaoxiong Wang, Yaxin Zhao, Aotian OuYang, Sizhu Suolang, Hongbo Zhou
Abstract Swine H1N1/2009 influenza is a highly infectious respiratory disease in pigs, which poses a great threat to pig production and human health. In this study, we investigated the global expression profiling of swine-encoded genes in response to swine H1N1/2009 influenza A virus (SIV-H1N1/2009) in newborn pig trachea (NPTr) cells. In total, 166 genes were found to be differentially expressed (DE) according to the gene microarray. After analyzing the DE genes which might affect the SIV-H1N1/2009 replication, we focused on polo-like kinase 3 (PLK3)...
October 24, 2023: Emerging Microbes & Infections
https://read.qxmd.com/read/37684042/loss-of-the-mitochondrial-protein-spd-3-elevates-plk-1-levels-and-dysregulates-mitotic-events
#13
JOURNAL ARTICLE
Yu-Zen Chen, Vitaly Zimyanin, Stefanie Redemann
In metazoans, Polo-like kinase (PLK1) controls several mitotic events including nuclear envelope breakdown, centrosome maturation, spindle assembly and progression through mitosis. Here we show that a mutation in the mitochondria-localized protein SPD-3 affects mitotic events by inducing elevated levels of PLK-1 in early Caenorhabditis elegans embryos. SPD-3 mutant embryos contain abnormally positioned mitotic chromosomes, show a delay in anaphase onset and asymmetrically disassemble the nuclear lamina. We found that more PLK-1 accumulated on centrosomes, nuclear envelope, nucleoplasm, and chromatin before NEBD, suggesting that PLK-1 overexpression is responsible for some of the observed mitotic phenotypes...
November 2023: Life Science Alliance
https://read.qxmd.com/read/37667329/ercc6l-facilitates-the-onset-of-mammary-neoplasia-and-promotes-the-high-malignance-of-breast-cancer-by-accelerating-the-cell-cycle
#14
JOURNAL ARTICLE
Hong Yang, Xiangjin Zhen, Yihui Yang, Yizhi Zhang, Sen Zhang, Yue Hao, Guanhua Du, Hongquan Wang, Bailin Zhang, Wan Li, Jinhua Wang
BACKGROUND: Breast cancer (BC) is the leading cause of morbidity and the second leading cause of death among female malignant tumors. Although available drugs have been approved for the corresponding breast cancer subtypes (ER-positive, HER2+ ) currently, there are still no effective targeted drugs or treatment strategies for metastatic breast cancer or triple-negative breast cancer that lack targets. Therefore, it is urgent to discover new potential targets. ERCC6L is an essential protein involved in chromosome separation during cell mitosis...
September 4, 2023: Journal of Experimental & Clinical Cancer Research: CR
https://read.qxmd.com/read/37640147/master-kinase-pdk1-in-tumorigenesis
#15
REVIEW
Nana Zheng, Jiaqi Wei, Depei Wu, Yang Xu, Jianping Guo
3-phosphoinositide-dependent protein kinase 1 (PDK1) is considered as master kinase regulating AGC kinase family members such as AKT, SGK, PLK, S6K and RSK. Although autophosphorylation regulates PDK1 activity, accumulating evidence suggests that PDK1 is manipulated by many other mechanisms, including S6K-mediated phosphorylation, and the E3 ligase SPOP-mediated ubiquitination and degradation. Dysregulation of these upstream regulators or downstream signals involves in cancer development, as PDK1 regulating cell growth, metastasis, invasion, apoptosis and survival time...
August 26, 2023: Biochimica et Biophysica Acta. Reviews on Cancer
https://read.qxmd.com/read/37570823/pentafuhalol-b-a-phlorotannin-from-brown-algae-strongly-inhibits-the-plk-1-overexpression-in-cancer-cells-as-revealed-by-computational-analysis
#16
JOURNAL ARTICLE
Waseem Ahmad Ansari, Safia Obaidur Rab, Mohammad Saquib, Aqib Sarfraz, Mohd Kamil Hussain, Mohd Sayeed Akhtar, Irfan Ahmad, Mohammad Faheem Khan
Polo-like kinase-1 (PLK-1) is an essential mitotic serine/threonine (Ser/Thr) kinase that belongs to the Polo-like kinase (PLK) family and is overexpressed in non-small cell lung cancer (NSCLC) via promotion of cell division. Therefore, PLK-1 may act as a promising target for the therapeutic cure of various cancers. Although a variety of anti-cancer drugs, both synthetic and naturally occurring, such as volasertib, onvansertib, thymoquinone, and quercetin, are available either alone or in combination with other therapies, they have limited efficacy, especially in the advanced stages of cancer...
August 3, 2023: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://read.qxmd.com/read/37477836/unique-asymmetric-distribution-of-phosphatidylserine-and-phosphatidylethanolamine-in-toxoplasma-gondii-revealed-by-nanoscale-analysis
#17
JOURNAL ARTICLE
Rikako Konishi, Kayoko Fukuda, Sayuri Kuriyama, Tatsunori Masatani, Xuenan Xuan, Akikazu Fujita
Toxoplasma gondii is a highly prevalent obligate apicomplexan parasite that is important in clinical and veterinary medicine. It is known that glycerophospholipids phosphatidylserine (PtdSer) and phosphatidylethanolamine (PtdEtn), especially their expression levels and flip-flops between cytoplasmic and exoplasmic leaflets, in the membrane of T. gondii play important roles in efficient growth in host mammalian cells, but their distributions have still not been determined because of technical difficulties in studying intracellular lipid distribution at the nanometer level...
July 21, 2023: Histochemistry and Cell Biology
https://read.qxmd.com/read/37467327/mechanisms-of-nuclear-pore-complex-disassembly-by-the-mitotic-polo-like-kinase-1-plk-1-in-c-elegans-embryos
#18
JOURNAL ARTICLE
Sylvia Nkombo Nkoula, Griselda Velez-Aguilera, Batool Ossareh-Nazari, Lucie Van Hove, Cristina Ayuso, Véronique Legros, Guillaume Chevreux, Laura Thomas, Géraldine Seydoux, Peter Askjaer, Lionel Pintard
The nuclear envelope, which protects and organizes the genome, is dismantled during mitosis. In the Caenorhabditis elegans zygote, nuclear envelope breakdown (NEBD) of the parental pronuclei is spatially and temporally regulated during mitosis to promote the unification of the maternal and paternal genomes. Nuclear pore complex (NPC) disassembly is a decisive step of NEBD, essential for nuclear permeabilization. By combining live imaging, biochemistry, and phosphoproteomics, we show that NPC disassembly is a stepwise process that involves Polo-like kinase 1 (PLK-1)-dependent and -independent steps...
July 21, 2023: Science Advances
https://read.qxmd.com/read/37293020/multivalent-coiled-coil-interactions-enable-full-scale-centrosome-assembly-and-strength
#19
Manolo U Rios, Małgorzata A Bagnucka, Bryan D Ryder, Beatriz Ferreira Gomes, Nicole Familiari, Kan Yaguchi, Matthew Amato, Łukasz A Joachimiak, Jeffrey B Woodruff
During mitotic spindle assembly, microtubules generate tensile stresses on pericentriolar material (PCM), the outermost layer of centrosomes. The molecular interactions that enable PCM to assemble rapidly and resist external forces are unknown. Here we use cross-linking mass spectrometry to identify interactions underlying supramolecular assembly of SPD-5, the main PCM scaffold protein in C. elegans . Crosslinks map primarily to alpha helices within the phospho-regulated region (PReM), a long C-terminal coiled-coil, and a series of four N-terminal coiled-coils...
May 18, 2023: bioRxiv
https://read.qxmd.com/read/37269004/a-polo-like-kinase-inhibitor-identified-by-computational-repositioning-attenuates-pulmonary-fibrosis
#20
JOURNAL ARTICLE
Takeshi Imakura, Seidai Sato, Kazuya Koyama, Hirohisa Ogawa, Takahiro Niimura, Kojin Murakami, Yuya Yamashita, Keiko Haji, Nobuhito Naito, Kozo Kagawa, Hiroshi Kawano, Yoshito Zamami, Keisuke Ishizawa, Yasuhiko Nishioka
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a fatal fibrotic lung disease with few effective therapeutic options. Recently, drug repositioning, which involves identifying novel therapeutic potentials for existing drugs, has been popularized as a new approach for the development of novel therapeutic reagents. However, this approach has not yet been fully utilized in the field of pulmonary fibrosis. METHODS: The present study identified novel therapeutic options for pulmonary fibrosis using a systematic computational approach for drug repositioning based on integration of public gene expression signatures of drug and diseases (in silico screening approach)...
June 2, 2023: Respiratory Research
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