36,021 results match your criteria tubulin


XMAP215 promotes microtubule catastrophe by disrupting the growing microtubule end.

J Cell Biol 2021 Oct 29;220(10). Epub 2021 Jul 29.

Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN.

The GTP-tubulin cap is widely accepted to protect microtubules against catastrophe. The GTP-cap size is thought to increase with the microtubule growth rate, presumably endowing fast-growing microtubules with enhanced stability. It is unknown what GTP-cap properties permit frequent microtubule catastrophe despite fast growth. Read More

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October 2021

HDAC6 inhibitor WT161 performs antitumor effect on osteosarcoma and synergistically interacts with 5-FU.

Authors:
Consolato Sergi

Biosci Rep 2021 Jul 29. Epub 2021 Jul 29.

Children's Hospital of Eastern Ontario, Edmonton, Canada.

An imbalance between protein aggregation and protein degradation may induce "stress" in the functionality of the endoplasmic reticulum. There are quality control mechanisms to minimize misfolding and to eliminate misfolded proteins before aggregation becomes lethal for the cell.  Proper protein folding and maturation is one of the crucial functions of the endoplasmic reticulum. Read More

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Regulation Of Microtubule: Current Concepts And Relevance To Neurodegenerative Diseases.

CNS Neurol Disord Drug Targets 2021 Jul 28. Epub 2021 Jul 28.

Neuroscience Division, Department of Pharmacology, ISF College of Pharmacy, Moga-142001 Punjab, India.

Neurodevelopmental disorders (NDDs) are abnormalities linked to neuronal structure and irregularities associated with the proliferation of cells, transportation, and differentiation. NDD also involves synaptic circuitry and neural network alterations known as synaptopathies. Microtubules (MTs) and MTs-associated proteins help to maintain neuronal health as well as their development. Read More

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Histone Deacetylase SIRT1 promotes loss of primary cilia in Cholangiocarcinoma.

Hepatology 2021 Jul 29. Epub 2021 Jul 29.

The Hormel Institute, University of Minnesota, Austin, MN, USA.

Background And Aims: Sirtuin 1 (SIRT1) is a complex NAD -dependent protein deacetylase known to act as a tumor promoter or suppressor in different cancers. Here, we describe a novel mechanism of SIRT1-induced destabilization of primary cilia in cholangiocarcinoma (CCA).

Approach And Results: A significant overexpression of SIRT1 was detected in human CCA specimens, and CCA cells including, HuCCT1, KMCH, and WITT1 as compared to normal cholangiocytes (H69 and NHC). Read More

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Fabrication of Hyaluronic Acid-Gold Nanoparticles with Chitosan to Modulate Neural Differentiation of Mesenchymal Stem Cells.

J Chin Med Assoc 2021 Jul 26. Epub 2021 Jul 26.

Neurological Institute Head of Department of Neurosurgery Taichung Veterans General Hospital, Taichung, Taiwan, ROC Department of Physical Therapy, Hung Kuang University, Taichung, Taiwan, ROC Basic Medical Education Center, Central Taiwan University of Science and Technology, Taichung, Taiwan, ROC Graduate Institute of Biomedical Science, China Medical University, Taichung, Taiwan, ROC Department of Occupational Safety and Health, China Medical University, Taichung, Taiwan, ROC Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan, ROC Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, ROC Blood Bank, Taichung Veterans General Hospital, Taichung, Taiwan, ROC Translational Medicine Research, China Medical University Hospital, Taichung, Taiwan, ROC.

Background: Chitosan (Chi) is a natural material which has been widely used in neural applications due to possessing better biocompatibility. In this research study, a novel of nanocomposites film based on Chitosan (Chi) with Hyaluronic Acid (HA), combined with varying amounts of gold nanoparticles (AuNPs) was created resulting in pure Chi, Chi-HA, Chi-HA-AuNPs (25 ppm) and Chi-HA-AuNPs (50 ppm).

Methods: This study focused on evaluating their effects on Mesenchymal Stem Cell (MSC) viability, colony formation and biocompatibility. Read More

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Exosomal TUBB3 mRNA expression of metastatic castration-resistant prostate cancer patients: Association with patient outcome under abiraterone.

Cancer Med 2021 Jul 28. Epub 2021 Jul 28.

Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

Background: To use ddPCR to quantify plasma exosomal class III β-tubulin (βIII-tubulin, TUBB3, encoded by the TUBB3 gene) mRNA expression in metastatic castration-resistant prostate cancer (mCRPC) patients, and study the association of this expression with abiraterone efficacy.

Methods: Blood samples were prospectively collected from 52 mCRPC patients using abiraterone as first-line therapy to measure plasma exosomal TUBB3 mRNA expression value before the initiation of abiraterone. Study endpoints were PSA response rate, PSA-progression-free survival (PSA-PFS), and overall survival (OS, from CRPC to death). Read More

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Preclinical and Early Clinical Development of PTC596, a Novel Small Molecule Tubulin-Binding Agent.

Mol Cancer Ther 2021 Jul 26. Epub 2021 Jul 26.

PTC Therapeutics (United States)

PTC596 is an investigational small molecule tubulin-binding agent. Unlike other tubulin-binding agents, PTC596 is orally bioavailable and is not a P-glycoprotein substrate. So as to characterize PTC596 to position the molecule for optimal clinical development, the interactions of PTC596 with tubulin using crystallography, its spectrum of preclinical in vitro anticancer activity, and its pharmacokinetic-pharmacodynamic relationship were investigated for efficacy in multiple preclinical mouse models of leiomyosarcomas and glioblastoma. Read More

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Effect of maternal overnutrition on predisposition to insulin resistance in the foal: Foal skeletal muscle development and insulin signaling.

Domest Anim Endocrinol 2021 Jul 2;77:106648. Epub 2021 Jul 2.

Department of Animal Science, Texas A&M University, College Station, Texas 77843. Electronic address:

Skeletal muscle plays an integral role in the ability of a horse to perform at high levels. Shifts in skeletal muscle development in response to maternal plane of nutrition may have substantial and lasting impacts on athletic performance and whole-body metabolism. Therefore, sixteen Quarter Horse mares were used in a completely randomized design and maintained at a body condition score (BCS) 6 until start of third trimester. Read More

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The tail wags the tubulin.

Dev Cell 2021 Jul;56(14):2007-2009

Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. Electronic address:

The C-terminal tail of tubulin influences microtubule assembly and stability. In this issue of Developmental Cell, Chen et al. combine in vitro experiments using recombinant tubulin with molecular dynamics simulations to provide molecular-level insights into the importance of α-tubulin tail and its post-translational modifications in microtubule assembly and stability. Read More

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HDAC6 Substrate Discovery Using Proteomics-Based Substrate Trapping: HDAC6 Deacetylates PRMT5 to Influence Methyltransferase Activity.

ACS Chem Biol 2021 Jul 27. Epub 2021 Jul 27.

Department of Chemistry, Wayne State University, 5101 Cass Avenue, Detroit, Michigan 48202, United States.

Histone deacetylase 6 (HDAC6) is upregulated in a variety of tumor cell lines and has been linked to many cellular processes, such as cell signaling, protein degradation, cell survival, and cell motility. HDAC6 is an enzyme that deacetylates the acetyllysine residues of protein substrates, and the discovery of HDAC6 substrates, including tubulin, has revealed many roles of HDAC6 in cell biology. Unfortunately, among the wide variety of acetylated proteins in the cell, only a few are verified as HDAC6 substrates, which limits the full characterization of HDAC6 cellular functions. Read More

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Trypanosoma vivax infection in sheep: Different patterns of virulence and pathogenicity associated with differentially expressed proteomes.

Vet Parasitol 2019 8;276S:100014. Epub 2019 Jun 8.

CIRAD, UMR ASTRE, F-34398 Montpellier, France; ASTRE, CIRAD, INRA, Univ. Montpellier (I-MUSE), Montpellier, France; INTERTRYP, CIRAD, IRD, Univ. Montpellier (I-MUSE), Montpellier, France.

Cattle trypanosomosis caused by Trypanosoma vivax is a widely distributed disease in Africa and Latin America. It causes significant losses in the livestock industry and is characterized by fluctuating parasitemia, anemia, fever, lethargy, and weight loss. In this study we evaluated the virulence (capacity to multiply inside the host and to modulate the host response) and pathogenicity (ability to produce disease and/or mortality) patterns of two T. Read More

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The structural, functional, and dynamic effect of Tau tubulin kinase1 upon a mutation: A neuro-degenerative hotspot.

J Cell Biochem 2021 Jul 23. Epub 2021 Jul 23.

Translational Bioinformatics Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India.

Alzheimer's disease (AD) is a progressive disorder that causes brain cells to degenerate and die. AD is one of the common causes of dementia that leads to a decline in thinking, behavioral and social skills that disrupts a person's ability to function independently. Tau-tubulin kinase1 (TTBK1) is a crucial disease regulating AD protein, which is majorly responsible for the phosphorylation and accumulation of tau protein at specific Serine/Threonine residues found in paired helical filaments, suggesting its role in tauopathy. Read More

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The developmental regulator PatD modulates assembly of the cell-division protein FtsZ in the cyanobacterium Anabaena sp. PCC 7120.

Environ Microbiol 2021 Jul 23. Epub 2021 Jul 23.

State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, the Chinese Academy of Sciences, Wuhan, Hubei, 430072, China.

FtsZ is a tubulin-like GTPase that polymerizes to initiate the process of cell division in bacteria. Heterocysts are terminally differentiated cells of filamentous cyanobacteria that have lost the capacity for cell division and in which the ftsZ gene is downregulated. However, mechanisms of FtsZ regulation during heterocyst differentiation have been scarcely investigated. Read More

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CNTs-CaP/chitosan-coated AZ91D magnesium alloy extract promoted rat dorsal root ganglia neuron growth via activating ERK signalling pathway.

Cell Biochem Funct 2021 Jul 22. Epub 2021 Jul 22.

Department of Neurology, First Affiliated Hospital of Harbin Medical University, Harbin, China.

Increasing attention has been paid on the application of biodegradable materials such as magnesium and its alloys in neuron repair. AZ91D magnesium alloy coated with carbon nanotubes (CNTs) and/or calcium phosphate (CaP)/chitosan (CS) was fabricated in this study. To evaluate the bioactivity of these AZ91D-based composites, the extracts were prepared by immersing samples in modified simulated body fluid (m-SBF) for 0, 2, 8, 16, 24, 34, 44, 60, or 90 days. Read More

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Discovery of novel trimethoxyphenylbenzo[d]oxazoles as dual tubulin/PDE4 inhibitors capable of inducing apoptosis at G2/M phase arrest in glioma and lung cancer cells.

Eur J Med Chem 2021 Jul 15;224:113700. Epub 2021 Jul 15.

Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China; Pharmacy Department, Zhujiang Hospital, Southern Medical University, Guangzhou, 510515, China. Electronic address:

To discover PDE4/tubulin dual inhibitors with novel skeleton structures, 7-trimethoxyphenylbenzo[d]oxazoles 4a-u and 4-trimethoxyphenylbenzo[d]oxazoles 5a-h were designed and synthesized by migrating the trimethoxyphenyl group of TH03 to the benzo[d]oxazole moiety. Among these compounds, approximately half of them displayed good antiproliferative activities against glioma (U251) and lung cancer (A549 and H460) cell lines. The structure-activity relationships of trimethoxyphenylbenzo[d]oxazoles led to the identification of 4r bearing indol-5-yl side-chain as a novel dual PDE4/tubulin inhibitor, which exhibited satisfactory antiproliferative activities against glioma (IC = 300 ± 50 nM) and lung cancer (average IC = 39. Read More

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Histone-deacetylase 8 drives the immune response and the growth of glioma.

Glia 2021 Jul 26. Epub 2021 Jul 26.

Department of Physiology and Pharmacology, Sapienza University, Rome, Italy.

Many epigenetic modifications occur in glioma, in particular the histone-deacetylase class proteins play a pivotal role in glioma development, driving the proliferation rate and the invasiveness of tumor cells, and modulating the tumor microenvironment. In this study, we evaluated the role of the histone deacetylase HDAC8 in the regulation of the immune response in glioma and tumor growth. We found that inhibition of HDAC8 by the specific inhibitor PCI-34051 reduces tumor volume in glioma mouse models. Read More

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A Wireframe DNA Cube - Antibody Conjugate for Targeted Delivery of Multiple Copies of Monomethyl Auristatin E.

Angew Chem Int Ed Engl 2021 Jul 26. Epub 2021 Jul 26.

Aarhus University: Aarhus Universitet, iNANO and Department of Chemistry, DENMARK.

In recent years, several antibody drug conjugates (ADC) have been accepted by the FDA as therapeutics against cancer. It is well-known that control of drug-to-antibody ratio (DAR) is vital for the success of an ADC, which inspires the advancement of better and simpler methods for tight control of DAR. We present the development of an antibody DNA wireframe cube conjugate for precise control of DAR. Read More

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Design, synthesis and biological evaluation of novel thiazole-naphthalene derivatives as potential anticancer agents and tubulin polymerisation inhibitors.

J Enzyme Inhib Med Chem 2021 Dec;36(1):1694-1702

College of Food Science and Technology, Shanghai Ocean University, Shanghai, China.

A novel series of thiazole-naphthalene derivatives as tubulin polymerisation inhibitors were designed, synthesised, and evaluated for the anti-proliferative activities. The majority of the tested compounds exhibited moderate to potent antiproliferative activity on the MCF-7 and A549 cancer cell lines. Among them, compound was found to be the most active compound with IC values of 0. Read More

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December 2021

Distinct roles of α- and β-tubulin polyglutamylation in controlling axonal transport and in neurodegeneration.

EMBO J 2021 Jul 26:e108498. Epub 2021 Jul 26.

Institut Curie, Université PSL, CNRS UMR3348, Orsay, France.

Tubulin polyglutamylation is a post-translational modification of the microtubule cytoskeleton, which is generated by a variety of enzymes with different specificities. The "tubulin code" hypothesis predicts that modifications generated by specific enzymes selectively control microtubule functions. Our recent finding that excessive accumulation of polyglutamylation in neurons causes their degeneration and perturbs axonal transport provides an opportunity for testing this hypothesis. Read More

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Melatonin Protects Against Mdivi-1-Induced Abnormal Spindle Assembly and Mitochondrial Superoxide Production During Porcine Oocyte Maturation.

Front Cell Dev Biol 2021 8;9:693969. Epub 2021 Jul 8.

Department of Biotechnology, College of Engineering, Daegu University, Gyeongsan, South Korea.

Mitochondrial division inhibitor 1 (Mdivi-1) reportedly provides a close connection between oocyte maturation and mitochondrial function in pigs. -acetyl-5-methoxy-tryptamine (melatonin) is known to be a representative antioxidant with the ability to rehabilitate meiotic maturation of porcine oocytes. However, the ability of melatonin to recover Mdivi-1-mediated disruption of spindle formation during meiotic maturation of porcine oocytes during maturation (IVM) has not been studied. Read More

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ROS/RNS Balancing, Aerobic Fermentation Regulation and Cell Cycle Control - a Complex Early Trait ('CoV-MAC-TED') for Combating SARS-CoV-2-Induced Cell Reprogramming.

Front Immunol 2021 7;12:673692. Epub 2021 Jul 7.

Functional Genomics and Bioinformatics Group, Department of Biochemistry and Molecular Biology, Federal University of Ceará, Fortaleza, Brazil.

In a perspective entitled 'From plant survival under severe stress to anti-viral human defense' we raised and justified the hypothesis that transcript level profiles of justified target genes established from somatic embryogenesis (SE) induction in plants as a reference compared to virus-induced profiles can identify differential virus signatures that link to harmful reprogramming. A standard profile of selected genes named 'ReprogVirus' was proposed for -scanning of early virus-induced reprogramming in critical primary infected cells/tissues as target trait. For data collection, the 'ReprogVirus platform' was initiated. Read More

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Identification of novel anti-cancer agents by the synthesis and cellular screening of a noscapine-based library.

Bioorg Chem 2021 Jun 30;115:105135. Epub 2021 Jun 30.

Department of Cellular Microbiology, University Hohenheim, 70599 Stuttgart, Germany. Electronic address:

Noscapine is a natural product first isolated from the opium poppy (Papaver somniferum L.) with anticancer properties. In this work, we report the synthesis and cellular screening of a noscapine-based library. Read More

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MYO1F regulates antifungal immunity by regulating acetylation of microtubules.

Proc Natl Acad Sci U S A 2021 Jul;118(30)

Key Laboratory of Molecular Biophysics of the Ministry of Education, National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China;

Opportunistic fungal infections have become one of the leading causes of death among immunocompromised patients, resulting in an estimated 1.5 million deaths each year worldwide. The molecular mechanisms that promote host defense against fungal infections remain elusive. Read More

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The histone chaperone Nrp1 is required for chromatin stability and nuclear division in Tetrahymena thermophila.

Epigenetics Chromatin 2021 Jul 23;14(1):34. Epub 2021 Jul 23.

Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Biotechnology, Shanxi University, 92 Wucheng Rd., Taiyuan, 030006, China.

Histone chaperones facilitate DNA replication and repair by promoting chromatin assembly, disassembly and histone exchange. Following histones synthesis and nucleosome assembly, the histones undergo posttranslational modification by different enzymes and are deposited onto chromatins by various histone chaperones. In Tetrahymena thermophila, histones from macronucleus (MAC) and micronucleus (MIC) have been comprehensively investigated, but the function of histone chaperones remains unclear. Read More

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Transcriptome Profile Analysis of Triple-Negative Breast Cancer Cells in Response to a Novel Cytostatic Tetrahydroisoquinoline Compared to Paclitaxel.

Int J Mol Sci 2021 Jul 19;22(14). Epub 2021 Jul 19.

Pharmaceutical Sciences Division, College of Pharmacy & Pharmaceutical Sciences, Institute of Public Health, Florida A&M University, Tallahassee, FL 32307, USA.

The absence of chemotherapeutic target hormone receptors in breast cancer is descriptive of the commonly known triple-negative breast cancer (TNBC) subtype. TNBC remains one of the most aggressive invasive breast cancers, with the highest mortality rates in African American women. Therefore, new drug therapies are continually being explored. Read More

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Regulation of Mitochondrial Respiration by VDAC Is Enhanced by Membrane-Bound Inhibitors with Disordered Polyanionic C-Terminal Domains.

Int J Mol Sci 2021 Jul 8;22(14). Epub 2021 Jul 8.

Center for Neutron Research, National Institute of Standards and Technology, Gaithersburg, MD 20899, USA.

The voltage-dependent anion channel (VDAC) is the primary regulating pathway of water-soluble metabolites and ions across the mitochondrial outer membrane. When reconstituted into lipid membranes, VDAC responds to sufficiently large transmembrane potentials by transitioning to gated states in which ATP/ADP flux is reduced and calcium flux is increased. Two otherwise unrelated cytosolic proteins, tubulin, and α-synuclein (αSyn), dock with VDAC by a novel mechanism in which the transmembrane potential draws their disordered, polyanionic C-terminal domains into and through the VDAC channel, thus physically blocking the pore. Read More

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Design, Hemiysnthesis, crystal structure and anticancer activity of 1, 2, 3-triazoles derivatives of totarol.

Bioorg Chem 2021 Jul 14;115:105165. Epub 2021 Jul 14.

Laboratoire de Synthèse Organique et Physico-Chimie Moléculaire, Département de Chimie, Faculté des Sciences, Semlalia, Université Cadi-Ayyad, B.P 2390, Marrakech 40001, Morocco. Electronic address:

A new series of diverse triazoles linked to the hydroxyl group of totarol were synthesized using click chemistry approach. The structures of these compounds were elucidated by HRMS, IR and NMR spectroscopy. The structure of compound 3 g was also confirmed by x-ray single crystal diffraction. Read More

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Molecular insight into how γ-TuRC makes microtubules.

J Cell Sci 2021 Jul 23;134(14). Epub 2021 Jul 23.

Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.

As one of four filament types, microtubules are a core component of the cytoskeleton and are essential for cell function. Yet how microtubules are nucleated from their building blocks, the αβ-tubulin heterodimer, has remained a fundamental open question since the discovery of tubulin 50 years ago. Recent structural studies have shed light on how γ-tubulin and the γ-tubulin complex proteins (GCPs) GCP2 to GCP6 form the γ-tubulin ring complex (γ-TuRC). Read More

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Loss of acentriolar MTOCs disrupts spindle pole Aurora A and assembly of the liquid-like meiotic spindle domain in oocytes.

J Cell Sci 2021 Jul 20;134(14). Epub 2021 Jul 20.

Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia,Athens, GA 30602, USA.

Oocyte-specific knockdown of pericentrin (PCNT) in transgenic (Tg) mice disrupts acentriolar microtubule-organizing center (aMTOC) formation, leading to spindle instability and error-prone meiotic division. Here, we show that PCNT-depleted oocytes lack phosphorylated Aurora A (pAURKA) at spindle poles, while overall levels are unaltered. To test aMTOC-associated AURKA function, metaphase II (MII) control (WT) and Tg oocytes were briefly exposed to a specific AURKA inhibitor (MLN8237). Read More

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A Fast and Efficient Approach to Obtaining High-Purity Glioma Stem Cell Culture.

Front Genet 2021 6;12:639858. Epub 2021 Jul 6.

Tongji University Cancer Center, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.

Glioma is the most common and malignant primary brain tumor. Patients with malignant glioma usually have a poor prognosis due to drug resistance and disease relapse. Cancer stem cells contribute to glioma initiation, progression, resistance, and relapse. Read More

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