Oryzalin, a dinitroaniline herbicide, binds to plant tubulin and inhibits microtubule polymerization in vitro

Planta ◽  
1987 ◽  
Vol 172 (2) ◽  
pp. 252-264 ◽  
Author(s):  
L. C. Morejohn ◽  
T. E. Bureau ◽  
J. Mol�-Bajer ◽  
A. S. Bajer ◽  
D. E. Fosket
Keyword(s):  
Microtubule Polymerization ◽  
Plant Tubulin

scholarly journals Regulation of Microtubule Dynamics by Bim1 and Bik1, the Budding Yeast Members of the EB1 and CLIP-170 Families of Plus-End Tracking Proteins

2010 ◽  
Vol 21 (12) ◽  
pp. 2013-2023 ◽  
Author(s):  
Kristina A. Blake-Hodek ◽  
Lynne Cassimeris ◽  
Tim C. Huffaker
Keyword(s):  
Budding Yeast ◽  
Family Members ◽  
Microtubule Dynamics ◽  
Microtubule Assembly ◽  
Microtubule Polymerization

Microtubule dynamics are regulated by plus-end tracking proteins (+TIPs), which bind microtubule ends and influence their polymerization properties. In addition to binding microtubules, most +TIPs physically associate with other +TIPs, creating a complex web of interactions. To fully understand how +TIPs regulate microtubule dynamics, it is essential to know the intrinsic biochemical activities of each +TIP and how +TIP interactions affect these activities. Here, we describe the activities of Bim1 and Bik1, two +TIP proteins from budding yeast and members of the EB1 and CLIP-170 families, respectively. We find that purified Bim1 and Bik1 form homodimers that interact with each other to form a tetramer. Bim1 binds along the microtubule lattice but with highest affinity for the microtubule end; however, Bik1 requires Bim1 for localization to the microtubule lattice and end. In vitro microtubule polymerization assays show that Bim1 promotes microtubule assembly, primarily by decreasing the frequency of catastrophes. In contrast, Bik1 inhibits microtubule assembly by slowing growth and, consequently, promoting catastrophes. Interestingly, the Bim1-Bik1 complex affects microtubule dynamics in much the same way as Bim1 alone. These studies reveal new activities for EB1 and CLIP-170 family members and demonstrate how interactions between two +TIP proteins influence their activities.

Ionic and nucleotide requirements for microtubule polymerization in vitro

Biochemistry ◽  
1975 ◽  
Vol 14 (13) ◽  
pp. 2996-3005 ◽  
Author(s):  
J. B. Olmsted ◽  
G. G. Borisy
Keyword(s):  
Microtubule Polymerization

scholarly journals Drosophila Nod Protein Binds Preferentially to the Plus Ends of Microtubules and Promotes Microtubule Polymerization In Vitro

2005 ◽  
Vol 16 (11) ◽  
pp. 5400-5409 ◽  
Author(s):  
Wei Cui ◽  
Lisa R. Sproul ◽  
Susan M. Gustafson ◽  
Heinrich J.G. Matthies ◽  
Susan P. Gilbert ◽  
...  
Keyword(s):  
Critical Role ◽  
Posterior Pole ◽  
Full Length ◽  
Dependent Manner ◽  
Female Meiosis ◽  
Truncated Form ◽  
Microtubule Polymerization ◽  
Preferential Binding ◽  
Collision Complexes

Nod, a nonmotile kinesinlike protein, plays a critical role in segregating achiasmate chromosomes during female meiosis. In addition to localizing to oocyte chromosomes, we show that functional full-length Nod-GFP (NodFL-GFP) localizes to the posterior pole of the oocyte at stages 9–10A, as does kinesin heavy chain (KHC), a plus end-directed motor. This posterior localization is abolished in grk mutants that no longer maintain the microtubule (MT) gradient in the oocyte. To test the hypothesis that Nod binds to the plus ends of MTs, we expressed and purified both full-length Nod (NodFL) and a truncated form of Nod containing only the motorlike domain (Nod318) from Escherichia coli and assessed their interactions with MTs in vitro. Both NodFL and Nod318 demonstrate preferential binding to the ends of the MTs, displaying a strong preference for binding to the plus ends. When Nod318-GFP:MT collision complexes were trapped by glutaraldehyde fixation, the preference for binding to plus ends versus minus ends was 17:1. NodFL and Nod318 also promote MT polymerization in vitro in a time-dependent manner. The observation that Nod is preferentially localized to the plus ends of MTs and stimulates MT polymerization suggests a mechanism for its function.

In vitro assembly of plant tubulin in the absence of microtubule-stabilizing reagents

2000 ◽  
Vol 45 (24) ◽  
pp. 2258-2263 ◽  
Author(s):  
Shanjin Huang ◽  
Haiyun Ren ◽  
Ming Yuan
Keyword(s):  
In Vitro Assembly ◽  
Plant Tubulin

Inhibition of microtubule polymerization by micromolar concentrations of mercury(II)

1984 ◽  
Vol 62 (9) ◽  
pp. 814-818 ◽  
Author(s):  
Robert A. B. Keates ◽  
Brian Yott
Keyword(s):  
Chelating Agents ◽  
Tetraacetic Acid ◽  
Microtubule Polymerization ◽  
Microtubule Protein ◽  
Molar Quantity ◽  
Total Hg ◽  
In Vitro Inhibition

Polymerization of microtubule protein in vitro has been tested in the presence of Hg2+. Inhibition occurs in the presence of Hg2+ concentrations lower than the molarity of the tubulin, even in the presence of 0.5 mM ethylenebis(oxyethylene-nitrilo)tetraacetic acid. The estimated concentration of free Hg2+ under these conditions is less than 10−20 M. The extent of inhibition is approximately stoichiometric in that the molar quantity of tubulin that fails to polymerize is comparable to or slightly greater than the total Hg2+ present as chelate. The affinity of the susceptible site for Hg2+ in microtubule protein must be exceptionally high and may not be protected by natural chelating agents in the cell. Preformed microtubules are rapidly depolymerized on addition of Hg2+ chelate. In vitro, inhibition is both prevented and rapidly reversed by 2-mercaptoethanol.

scholarly journals Purification of functional Plasmodium falciparum tubulin allows for the identification of parasite-specific microtubule inhibitors

2021 ◽  
Author(s):  
William Graham Hirst ◽  
Dominik Fachet ◽  
Benno Kuropka ◽  
Christoph Weise ◽  
Kevin J Saliba ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Drug Targets ◽  
Cytoskeletal Proteins ◽  
Microtubule Inhibitors ◽  
Microtubule Polymerization ◽  
Molecular Building Block ◽  
Structural Divergence ◽  
Microtubule Growth ◽  
Exciting Possibility

Cytoskeletal proteins are essential for parasite proliferation, growth, and transmission, and therefore represent promising drug targets. While αβ-tubulin, the molecular building block of microtubules, is an established drug target in a variety of cancers, we still lack substantial knowledge of the biochemistry of parasite tubulins, which would allow us to exploit the structural divergence between parasite and human tubulins. Indeed, mechanistic insights have been limited by the lack of purified, functional parasite tubulin. In this study, we isolated Plasmodium falciparum tubulin that is assembly-competent and shows specific microtubule dynamics in vitro. We further present mechanistic evidence that two compounds selectively interact with parasite over host microtubules and inhibit Plasmodium microtubule polymerization at substoichiometric compound concentrations. The ability of compounds to selectively disrupt protozoan microtubule growth without affecting human microtubules provides the exciting possibility for the targeted development of novel antimalarials.

scholarly journals Ensconsin/Map7 promotes microtubule growth and centrosome separation in Drosophila neural stem cells

2014 ◽  
Vol 204 (7) ◽  
pp. 1111-1121 ◽  
Author(s):  
Emmanuel Gallaud ◽  
Renaud Caous ◽  
Aude Pascal ◽  
Franck Bazile ◽  
Jean-Philippe Gagné ◽  
...  
Keyword(s):  
Mitotic Spindle ◽  
Spindle Assembly ◽  
Microtubule Associated Proteins ◽  
Microtubule Polymerization ◽  
Sister Chromatids ◽  
Centrosome Separation ◽  
Associated Proteins ◽  
Microtubule Growth ◽  
Mitotic Spindle Assembly

The mitotic spindle is crucial to achieve segregation of sister chromatids. To identify new mitotic spindle assembly regulators, we isolated 855 microtubule-associated proteins (MAPs) from Drosophila melanogaster mitotic or interphasic embryos. Using RNAi, we screened 96 poorly characterized genes in the Drosophila central nervous system to establish their possible role during spindle assembly. We found that Ensconsin/MAP7 mutant neuroblasts display shorter metaphase spindles, a defect caused by a reduced microtubule polymerization rate and enhanced by centrosome ablation. In agreement with a direct effect in regulating spindle length, Ensconsin overexpression triggered an increase in spindle length in S2 cells, whereas purified Ensconsin stimulated microtubule polymerization in vitro. Interestingly, ensc-null mutant flies also display defective centrosome separation and positioning during interphase, a phenotype also detected in kinesin-1 mutants. Collectively, our results suggest that Ensconsin cooperates with its binding partner Kinesin-1 during interphase to trigger centrosome separation. In addition, Ensconsin promotes microtubule polymerization during mitosis to control spindle length independent of Kinesin-1.

Cellular Senescence-Inducing Small Molecules for Cancer Treatment

2019 ◽  
Vol 19 (2) ◽  
pp. 109-119 ◽  
Author(s):  
Peng Liu ◽  
Ziwen Lu ◽  
Yanfang Wu ◽  
Dongsheng Shang ◽  
Zhicong Zhao ◽  
...  
Keyword(s):  
Cellular Senescence ◽  
Drug Induced ◽  
Replication Process ◽  
Microtubule Polymerization ◽  
Response To Chemotherapy ◽  
Anti Cancer ◽  
Secretory Phenotype ◽  
Novel Therapeutic Strategies

Recently, the chemotherapeutic drug-induced cellular senescence has been considered a promising anti-cancer approach. The drug-induced senescence, which shows both similar and different hallmarks from replicative and oncogene-induced senescence, was regarded as a key determinant of tumor response to chemotherapy in vitro and in vivo. To date, an amount of effective chemotherapeutic drugs that can evoke senescence in cancer cells have been reported. The targets of these drugs differ substantially, including senescence signaling pathways, DNA replication process, DNA damage pathways, epigenetic modifications, microtubule polymerization, senescence-associated secretory phenotype (SASP), and so on. By summarizing senescence-inducing small molecule drugs together with their specific traits and corresponding mechanisms, this review is devoted to inform scientists to develop novel therapeutic strategies against cancer through inducing senescence.

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