keyword
https://read.qxmd.com/read/38321961/lsd1-controls-a-nuclear-checkpoint-in-wnt-%C3%AE-catenin-signaling-to-regulate-muscle-stem-cell-self-renewal
#21
JOURNAL ARTICLE
Sandrine Mouradian, Delia Cicciarello, Nicolas Lacoste, Valérie Risson, Francesca Berretta, Fabien Le Grand, Nicolas Rose, Thomas Simonet, Laurent Schaeffer, Isabella Scionti
The Wnt/β-Catenin pathway plays a key role in cell fate determination during development and in adult tissue regeneration by stem cells. These processes involve profound gene expression and epigenome remodeling and linking Wnt/β-Catenin signaling to chromatin modifications has been a challenge over the past decades. Functional studies of the lysine demethylase LSD1/KDM1A converge to indicate that this epigenetic regulator is a key regulator of cell fate, although the extracellular cues controlling LSD1 action remain largely unknown...
February 7, 2024: Nucleic Acids Research
https://read.qxmd.com/read/38319231/targeting-tacc3-induces-immunogenic-cell-death-and-enhances-t-dm1-response-in-her2-positive-breast-cancer
#22
JOURNAL ARTICLE
Mustafa Emre Gedik, Ozge Saatci, Nathaniel Oberholtzer, Meral Uner, Ozge Akbulut-Caliskan, Metin Cetin, Mertkaya Aras, Kubra Ibis, Burcu Caliskan, Erden Banoglu, Stefan Wiemann, Ayşegül Üner, Sercan Aksoy, Shikhar Mehrotra, Ozgur Sahin
Trastuzumab emtansine (T-DM1) was the first and one of the most successful antibody-drug conjugates (ADCs) approved for treating refractory HER2-positive breast cancer. Despite its initial clinical efficacy, resistance is unfortunately common, necessitating approaches to improve response. Here, we found that in sensitive cells T-DM1 induced spindle assembly checkpoint (SAC)-dependent immunogenic cell death (ICD), an immune-priming form of cell death. The payload of T-DM1 mediated ICD by inducing eIF2α phosphorylation, surface exposure of calreticulin, ATP and HMGB1 release, and secretion of ICD-related cytokines, all of which were lost in resistance...
February 6, 2024: Cancer Research
https://read.qxmd.com/read/38308077/calreticulin-and-jak2v617f-driver-mutations-induce-distinct-mitotic-defects-in-myeloproliferative-neoplasms
#23
JOURNAL ARTICLE
Kristin Holl, Nicolas Chatain, Susanne Krapp, Julian Baumeister, Tiago Maié, Sarah Schmitz, Anja Scheufen, Nathalie Brock, Steffen Koschmieder, Daniel Moreno-Andrés
Myeloproliferative neoplasms (MPNs) encompass a diverse group of hematologic disorders driven by mutations in JAK2, CALR, or MPL. The prevailing working model explaining how these driver mutations induce different disease phenotypes is based on the decisive influence of the cellular microenvironment and the acquisition of additional mutations. Here, we report increased levels of chromatin segregation errors in hematopoietic cells stably expressing CALRdel52 or JAK2V617F mutations. Our investigations employing murine 32DMPL and human erythroleukemic TF-1MPL cells demonstrate a link between CALRdel52 or JAK2V617F expression and a compromised spindle assembly checkpoint (SAC), a phenomenon contributing to error-prone mitosis...
February 2, 2024: Scientific Reports
https://read.qxmd.com/read/38294668/advanced-maternal-age-affects-the-cryosusceptibility-of-ovulated-but-not-in-vitro-matured-mouse-oocytes
#24
JOURNAL ARTICLE
Akshatha Daddangadi, Shubhashree Uppangala, Shama Prasada Kabekkodu, Nadeem Khan G, Guruprasad Kalthur, Riccardo Talevi, Satish Kumar Adiga
Oocyte cryopreservation is offered to women of various age groups for both health and social reasons. Oocytes derived from either controlled ovarian stimulation or in vitro maturation (IVM) are cryopreserved via vitrification. As maternal age is a significant determinant of oocyte quality, there is limited data on the age-related susceptibility of oocytes to the vitrification-warming procedure alone or in conjunction with IVM. In the present study, metaphase II oocytes obtained from 2, 6, 9, and 12 month old Swiss albino mice either by superovulation or IVM were used...
January 31, 2024: Reproductive Sciences
https://read.qxmd.com/read/38293145/an-unconventional-regulatory-circuitry-involving-aurora-b-controls-anaphase-onset-and-error-free-chromosome-segregation-in-trypanosomes
#25
Daniel Ballmer, Hua Jane Lou, Midori Ishii, Benjamin E Turk, Bungo Akiyoshi
Accurate chromosome segregation during mitosis requires that all chromosomes establish stable bi-oriented attachments with the spindle apparatus. Kinetochores form the interface between chromosomes and spindle microtubules and as such are under tight control by complex regulatory circuitry. As part of the chromosomal passenger complex (CPC), the Aurora B kinase plays a central role within this circuitry by destabilizing improper kinetochore-microtubule attachments and relaying the attachment status to the spindle assembly checkpoint, a feedback control system that delays the onset of anaphase by inhibiting the anaphase-promoting complex/cyclosome...
January 20, 2024: bioRxiv
https://read.qxmd.com/read/38279026/weakened-apc-c-activity-at-mitotic-exit-drives-cancer-vulnerability-to-kif18a-inhibition
#26
JOURNAL ARTICLE
Colin R Gliech, Zhong Y Yeow, Daniel Tapias-Gomez, Yuchen Yang, Zhaoyu Huang, Andréa E Tijhuis, Diana Cj Spierings, Floris Foijer, Grace Chung, Nuria Tamayo, Zahra Bahrami-Nejad, Patrick Collins, Thong T Nguyen, Andres Plata Stapper, Paul E Hughes, Marc Payton, Andrew J Holland
The efficacy of current antimitotic cancer drugs is limited by toxicity in highly proliferative healthy tissues. A cancer-specific dependency on the microtubule motor protein KIF18A therefore makes it an attractive therapeutic target. Not all cancers require KIF18A, however, and the determinants underlying this distinction remain unclear. Here, we show that KIF18A inhibition drives a modest and widespread increase in spindle assembly checkpoint (SAC) signaling from kinetochores which can result in lethal mitotic delays...
January 26, 2024: EMBO Journal
https://read.qxmd.com/read/38276821/sirna-mediated-bmaurora-b-depletion-impedes-the-formation-of-holocentric-square-spindles-in-silkworm-metaphase-bmn4-cells
#27
JOURNAL ARTICLE
Bing Zhang, Camilo Ayra-Pardo, Xiaoning Liu, Meiting Song, Dandan Li, Yunchao Kan
Silkworm ovary-derived BmN4 cells rely on chromatin-induced spindle assembly to form microtubule-based square mitotic spindles that ensure accurate segregation of holocentric chromosomes during cell division. The chromosome passenger protein Aurora B regulates chromosomal condensation and segregation, spindle assembly checkpoint activation, and cytokinesis; however, its role in holocentric organisms needs further clarification. This study examined the architecture and dynamics of spindle microtubules during prophase and metaphase in BmN4 cells and those with siRNA-mediated BmAurora B knockdown using immunofluorescence labeling...
January 19, 2024: Insects
https://read.qxmd.com/read/38258067/maximizing-anticancer-response-with-mps1-and-cenpe-inhibition-alongside-apoptosis-induction
#28
JOURNAL ARTICLE
Bárbara Pinto, João P N Silva, Patrícia M A Silva, Daniel José Barbosa, Bruno Sarmento, Juliana Carvalho Tavares, Hassan Bousbaa
Antimitotic compounds, targeting key spindle assembly checkpoint (SAC) components (e.g., MPS1, Aurora kinase B, PLK1, KLP1, CENPE), are potential alternatives to microtubule-targeting antimitotic agents (e.g., paclitaxel) to circumvent resistance and side effects associated with their use. They can be classified into mitotic blockers, causing SAC-induced mitotic arrest, or mitotic drivers, pushing cells through aberrant mitosis by overriding SAC. These drugs, although advancing to clinical trials, exhibit unsatisfactory cancer treatment outcomes as monotherapy, probably due to variable cell fate responses driven by cyclin B degradation and apoptosis signal accumulation networks...
December 29, 2023: Pharmaceutics
https://read.qxmd.com/read/38242874/cox6c-expression-driven-by-copy-amplification-of-8q22-2-regulates-cell-proliferation-via-mediation-of-mitosis-by-ros-ampk-signaling-in-lung-adenocarcinoma
#29
JOURNAL ARTICLE
Shuanghui Liu, Fanggui Shao, Yourong Wang, Yurui Zhang, Hongjia Yu, Ningxin Zhang, Lan He, Qingran Kong, Hao Jiang, Zhixiong Dong
Copy number variations (CNVs) play a vital role in regulating genes expression and tumorigenesis. We explored the copy number alterations in early-stage lung adenocarcinoma using high-throughput sequencing and nucleic acid flight mass spectrometry technology, and found that 8q22.1-22.2 is frequently amplified in lung adenocarcinoma tissues. COX6C localizes on the region and its expression is notably enhanced that driven by amplification in lung adenocarcinoma. Knockdown of COX6C significantly inhibits the cell proliferation, and induces S-G2/M cell cycle arrest, mitosis deficiency and apoptosis...
January 19, 2024: Cell Death & Disease
https://read.qxmd.com/read/38234763/contribution-of-cenp-f-to-foxm1-mediated-discordant-centromere-and-kinetochore-transcriptional-regulation
#30
Sakshi Khurana, Daniel R Foltz
Proper chromosome segregation is required to ensure genomic and chromosomal stability. The centromere is a unique chromatin domain present throughout the cell cycle on each chromosome defined by the CENP-A nucleosome. Centromeres (CEN) are responsible for recruiting the kinetochore (KT) during mitosis, ultimately regulating spindle attachment and mitotic checkpoint function. Upregulation of many genes that encode the CEN/KT proteins is commonly observed in cancer. Here, we show although that FOXM1 occupies the promoters of many CEN/KT genes with MYBL2, occupancy is insufficient alone to drive the FOXM1 correlated transcriptional program...
December 27, 2023: bioRxiv
https://read.qxmd.com/read/38221646/transient-excited-states-of-the-metamorphic-protein-mad2-and-their-implications-for-function
#31
JOURNAL ARTICLE
Shefali Jain, Ashok Sekhar
The spindle checkpoint complex is a key surveillance mechanism in cell division that prevents premature separation of sister chromatids. Mad2 is an integral component of this spindle checkpoint complex that recognizes cognate substrates such as Mad1 and Cdc20 in its closed (C-Mad2) conformation by fastening a "seatbelt" around short peptide regions that bind to the substrate recognition site. Mad2 is also a metamorphic protein that adopts not only the fold found in C-Mad2, but also a structurally distinct open conformation (O-Mad2) which is incapable of binding substrates...
January 14, 2024: Proteins
https://read.qxmd.com/read/38213208/a-pan-cancer-analysis-of-the-immunological-and-prognostic-role-of-bub1-mitotic-checkpoint-serine-threonine-kinase-b-bub1b-in-human-tumors
#32
JOURNAL ARTICLE
Wenjie Huang, Zhisong Chen, Yongmei Tang, Jingjing Li, Li Fan
BACKGROUND: BUB1 mitotic checkpoint serine/threonine kinase B (BUB1B) is a member of the spindle assembly checkpoint family and is related to cancer disease progression, invasion, metastasis, and functional promotion of angiogenesis. Several studies have noted that the BUB1B gene is frequently upregulated in various types of cancers. However, the expression patterns of BUB1B across different cancer types and its diagnostic and prognostic potential have not been investigated from a pan-cancer perspective...
January 1, 2024: Clinical Laboratory
https://read.qxmd.com/read/38203427/hexavalent-chromium-targets-securin-to-drive-numerical-chromosome-instability-in-human-lung-cells
#33
JOURNAL ARTICLE
Jennifer H Toyoda, Julieta Martino, Rachel M Speer, Idoia Meaza, Haiyan Lu, Aggie R Williams, Alicia M Bolt, Joseph Calvin Kouokam, Abou El-Makarim Aboueissa, John Pierce Wise
Hexavalent chromium [Cr(VI)] is a known human lung carcinogen with widespread exposure in environmental and occupational settings. Despite well-known cancer risks, the molecular mechanisms of Cr(VI)-induced carcinogenesis are not well understood, but a major driver of Cr(VI) carcinogenesis is chromosome instability. Previously, we reported Cr(VI) induced numerical chromosome instability, premature centriole disengagement, centrosome amplification, premature centromere division, and spindle assembly checkpoint bypass...
December 23, 2023: International Journal of Molecular Sciences
https://read.qxmd.com/read/38180477/multimerization-of-a-disordered-kinetochore-protein-promotes-accurate-chromosome-segregation-by-localizing-a-core-dynein-module
#34
JOURNAL ARTICLE
Jessica M McGory, Vikash Verma, Dylan M Barcelos, Thomas J Maresca
Kinetochores connect chromosomes and spindle microtubules to maintain genomic integrity through cell division. Crosstalk between the minus-end directed motor dynein and kinetochore-microtubule attachment factors promotes accurate chromosome segregation by a poorly understood pathway. Here, we identify a linkage between the intrinsically disordered protein Spc105 (KNL1 orthologue) and dynein using an optogenetic oligomerization assay. Core pools of the checkpoint protein BubR1 and the adaptor complex RZZ contribute to the linkage...
March 4, 2024: Journal of Cell Biology
https://read.qxmd.com/read/38170753/a-coadapted-knl1-and-spindle-assembly-checkpoint-axis-orchestrates-precise-mitosis-in-arabidopsis
#35
JOURNAL ARTICLE
Xingguang Deng, Ying He, Xiaoya Tang, Xianghong Liu, Yuh-Ru Julie Lee, Bo Liu, Honghui Lin
The kinetochore scaffold 1 (KNL1) protein recruits spindle assembly checkpoint (SAC) proteins to ensure accurate chromosome segregation during mitosis. Despite such a conserved function among eukaryotic organisms, its molecular architectures have rapidly evolved so that the functional mode of plant KNL1 is largely unknown. To understand how SAC signaling is regulated at kinetochores, we characterized the function of the KNL1 gene in Arabidopsis thaliana . The KNL1 protein was detected at kinetochores throughout the mitotic cell cycle, and null knl1 mutants were viable and fertile but exhibited severe vegetative and reproductive defects...
January 9, 2024: Proceedings of the National Academy of Sciences of the United States of America
https://read.qxmd.com/read/38166399/fission-yeast-wee1-is-required-for-stable-kinetochore-microtubule-attachment
#36
JOURNAL ARTICLE
Masahiro Takado, Takaharu G Yamamoto, Yuji Chikashige, Tomohiro Matsumoto
Wee1 is a cell cycle regulator that phosphorylates Cdk1/Cdc2 and inhibits G2/M transition. Loss of Wee1 in fission yeast results in an early onset of mitosis. Interestingly, we found that cells lacking Wee1 require the functional spindle checkpoint for their viability. Genetic analysis indicated that the requirement is not attributable to the early onset of mitosis. Live-cell imaging revealed that some kinetochores are not attached or bioriented in the wee1 mutant. Furthermore, Mad2, a component of the spindle checkpoint known to recognize unattached kinetochores, accumulates in the vicinity of the spindle, representing activation of the spindle checkpoint in the mutant...
January 2024: Open Biology
https://read.qxmd.com/read/38162070/-prognostic-value-of-pcmt1-expression-in-gastric-cancer-and-its-regulatory-effect-on-spindle-assembly-checkpoints
#37
JOURNAL ARTICLE
Yueyue Wang, Min Zhang, Zhen Zhang, Bohan Li, Ju Huang, Jing Li, Zhijun Geng, Xiaofeng Zhang, Xue Song, Lian Wang, Lugen Zuo, Jianguo Hu
OBJECTIVE: The study was conducted to investigate the expression of protein-L-isoaspartate (D-aspartate) O-methyltransferase (PCMT1) in gastric cancer and its effect on the prognosis, and to analyze its potential mechanism. METHODS: UALCAN, a cancer data analysis platform, was used to conduct online analysis of the expression of PCMT1 in gastric cancer tissues. Through the Database for Annotation, Visualization and Integrated Discovery (DAVID), Gene Ontology (GO) annotation and signaling pathway enrichment by Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed to analyze the possible functions and signaling pathways...
November 20, 2023: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://read.qxmd.com/read/38159497/discovery-of-a-potent-and-selective-covalent-threonine-tyrosine-kinase-ttk-inhibitor
#38
JOURNAL ARTICLE
Yaoliang Sun, Zhiwen Chen, Guobin Liu, Xiaoai Chen, Zihan Shi, Huixu Feng, Lei Yu, Guodong Li, Ke Ding, He Huang, Zhang Zhang, Shilin Xu
Threonine tyrosine kinase (TTK) is a critical component of the spindle assembly checkpoint and plays a pivotal role in mitosis. TTK has been identified as a potential therapeutic target for human cancers. Here, we describe our design, synthesis and evaluation of a class of covalent TTK inhibitors, exemplified by 16 (SYL1073). Compound 16 potently inhibits TTK kinase with an IC50 of 0.016 μM and displays improved selectivity in a panel of kinases. Mass spectrometry analysis reveals that 16 covalently binds to the C604 cysteine residue in the hinge region of the TTK kinase domain...
December 25, 2023: Bioorganic Chemistry
https://read.qxmd.com/read/38136917/c-type-natriuretic-peptide-pre-treatment-improves-maturation-rate-of-goat-oocytes-by-maintaining-transzonal-projections-spindle-morphology-and-mitochondrial-function
#39
JOURNAL ARTICLE
Rui Xu, Menghao Pan, Lu Yin, Yiqian Zhang, Yaju Tang, Sihai Lu, Yan Gao, Qiang Wei, Bin Han, Baohua Ma
C-type natriuretic peptide (CNP) is a peptide molecule naturally found in follicles and can be used to extend meiotic resumption and enhance the potential for oocytes to develop. However, the mechanism by which CNP improves goat oocyte quality remains unclear. In this study, cumulus-oocyte complexes (COCs) from goats were pre-treated with CNP prior to IVM, and the results showed that pre-treatment with CNP enhanced goat oocyte maturation. First, we discovered that CNP maintained communication between cumulus cells and oocytes by regulating the transzonal projections (TZPs)...
December 16, 2023: Animals: An Open Access Journal From MDPI
https://read.qxmd.com/read/38136322/inhibition-of-survivin-homodimerization-decreases-neuroblastoma-cell-growth
#40
JOURNAL ARTICLE
Carmen Dorneburg, Celimene Galiger, Giovanna L Stadler, Mike-Andrew Westhoff, Volker Rasche, Thomas F E Barth, Klaus-Michael Debatin, Christian Beltinger
Increased expression of BIRC5/survivin, a crucial regulator of the mitotic spindle checkpoint, is associated with poor prognosis in neuroblastoma (NB), the most common extracranial tumor of childhood. Transcriptional inhibitors of survivin have been tested in adult cancers and inhibitors of survivin homodimerization are emerging. We compared genetic inhibition of survivin transcription with the inhibition of survivin homodimerization by S12 and LQZ-7I, chosen from a larger panel of survivin dimerization inhibitors with activity against NB cells...
December 9, 2023: Cancers
keyword
keyword
49963
2
3
Fetch more papers »
Fetching more papers... Fetching...
Remove bar
Read by QxMD icon Read
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"

We want to hear from doctors like you!

Take a second to answer a survey question.