A Novel Non-Genomic Action of Estradiol (E) and Testosterone (T): Regulators of Microtubule Polymerization

2003 ◽  
pp. 147-156
Author(s):  
Victor D. Ramirez ◽  
Jingjing Liu Kipp
Keyword(s):  
Microtubule Polymerization

Towards further Understanding the Structural Requirements of Combretastatin- like Chalcones as Inhibitors of Microtubule Polymerization

2020 ◽  
Vol 16 (2) ◽  
pp. 155-166
Author(s):  
Naveen Dhingra ◽  
Anand Kar ◽  
Rajesh Sharma
Keyword(s):  
Three Dimensional ◽  
3D Qsar ◽  
Docking Study ◽  
Structure Activity Relationship ◽  
Docking Studies ◽  
Activity Relationship ◽  
Structural Requirement ◽  
Ligand Interaction ◽  
Microtubule Polymerization ◽  
Structure Activity

Background: Microtubules are dynamic filamentous cytoskeletal structures which play several key roles in cell proliferation and trafficking. They are supposed to contribute in the development of important therapeutic targeting tumor cells. Chalcones are important group of natural compounds abundantly found in fruits & vegetables that are known to possess anticancer activity. We have used QSAR and docking studies to understand the structural requirement of chalcones for understanding the mechanism of microtubule polymerization inhibition. Methods: Three dimensional (3D) QSAR (CoMFA and CoMSIA), pharmacophore mapping and molecular docking studies were performed for the generation of structure activity relationship of combretastatin-like chalcones through statistical models and contour maps. Results: Structure activity relationship revealed that substitution of electrostatic, steric and donor groups may enhance the biological activity of compounds as inhibitors of microtubule polymerization. From the docking study, it was clear that compounds bind at the active site of tubulin protein. Conclusion: The given strategies of modelling could be an encouraging way for designing more potent compounds as well as for the elucidation of protein-ligand interaction.

scholarly journals Challenging the Role of Microtubules in Tobacco Mosaic Virus Movement by Drug Treatments Is Disputable

2006 ◽  
Vol 80 (13) ◽  
pp. 6712-6715 ◽  
Author(s):  
Mark Seemanpillai ◽  
Rabab Elamawi ◽  
Christophe Ritzenthaler ◽  
Manfred Heinlein
Keyword(s):  
Tobacco Mosaic Virus ◽  
Mosaic Virus ◽  
Movement Protein ◽  
Viral Rna ◽  
Virus Movement ◽  
Direct Role ◽  
Microtubule Inhibitors ◽  
Microtubule Polymerization ◽  
Drug Treatments

ABSTRACT The movement protein (MP) of Tobacco mosaic virus interacts with microtubules during infection. Although this interaction is correlated with the function of MP in the cell-to-cell transport of viral RNA, a direct role of microtubules in the movement process was recently challenged by studies involving the treatment of plants with inhibitors of microtubule polymerization. Here, we report evidence suggesting that such treatments may not efficiently disrupt all microtubules. Thus, results obtained from studies using microtubule inhibitors may have to remain open to interpretation with regard to the involvement of microtubules in viral RNA trafficking.

Antimitotic Antifungal Compound Benomyl Inhibits Brain Microtubule Polymerization and Dynamics and Cancer Cell Proliferation at Mitosis, by Binding to a Novel Site in Tubulin†

Biochemistry ◽  
2004 ◽  
Vol 43 (21) ◽  
pp. 6645-6655 ◽  
Author(s):  
Kamlesh Gupta ◽  
Jamie Bishop ◽  
Austin Peck ◽  
Julie Brown ◽  
Leslie Wilson ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cancer Cell ◽  
Antifungal Compound ◽  
Cancer Cell Proliferation ◽  
Microtubule Polymerization

scholarly journals The Adenomatous Polyposis Coli Protein Is Required for the Formation of Robust Spindles Formed in CSF Xenopus Extracts

2004 ◽  
Vol 15 (6) ◽  
pp. 2978-2991 ◽  
Author(s):  
Dina Dikovskaya ◽  
Ian P. Newton ◽  
Inke S. Näthke
Keyword(s):  
Adenomatous Polyposis Coli ◽  
Chromosomal Instability ◽  
Adenomatous Polyposis ◽  
Mitotic Spindles ◽  
Polyposis Coli ◽  
Adenomatous Polyposis Coli Protein ◽  
Microtubule Binding ◽  
Microtubule Polymerization ◽  
Large N ◽  
Apc Protein

Mutations in the adenomatous polyposis coli (APC) protein occur early in colon cancer and correlate with chromosomal instability. Here, we show that depletion of APC from cystostatic factor (CSF) Xenopus extracts leads to a decrease in microtubule density and changes in tubulin distribution in spindles and asters formed in such extracts. Addition of full-length APC protein or a large, N-terminally truncated APC fragment to APC-depleted extracts restored normal spindle morphology and the intact microtubule-binding site of APC was necessary for this rescue. These data indicate that the APC protein plays a role in the formation of spindles that is dependent on its effect on microtubules. Spindles formed in cycled extracts were not sensitive to APC depletion. In CSF extracts, spindles predominantly formed from aster-like intermediates, whereas in cycled extracts chromatin was the major site of initial microtubule polymerization. These data suggest that APC is important for centrosomally driven spindle formation, which was confirmed by our finding that APC depletion reduced the size of asters nucleated from isolated centrosomes. We propose that lack of microtubule binding in cancer-associated mutations of APC may contribute to defects in the assembly of mitotic spindles and lead to missegregation of chromosomes.

scholarly journals Sensory neuropathy in progressive motor neuronopathy(pmn)mice is associated with defects in microtubule polymerization and axonal transport

2016 ◽  
Vol 27 (4) ◽  
pp. 459-471 ◽  
Author(s):  
Michael K. Schäfer ◽  
Sarah Bellouze ◽  
Arnaud Jacquier ◽  
Sébastien Schaller ◽  
Laurence Richard ◽  
...  
Keyword(s):  
Axonal Transport ◽  
Sensory Neuropathy ◽  
Microtubule Polymerization

scholarly journals EB1 and EB3 regulate microtubule minus end organization and Golgi morphology

2017 ◽  
Vol 216 (10) ◽  
pp. 3179-3198 ◽  
Author(s):  
Chao Yang ◽  
Jingchao Wu ◽  
Cecilia de Heus ◽  
Ilya Grigoriev ◽  
Nalan Liv ◽  
...  
Keyword(s):  
Cell Division ◽  
Cell Lines ◽  
Protein Complexes ◽  
Focal Adhesions ◽  
Microtubule Organization ◽  
The Core ◽  
Microtubule Polymerization ◽  
Golgi Membranes ◽  
Core Components ◽  
Knockout Technology

End-binding proteins (EBs) are the core components of microtubule plus end tracking protein complexes, but it is currently unknown whether they are essential for mammalian microtubule organization. Here, by using CRISPR/Cas9-mediated knockout technology, we generated stable cell lines lacking EB2 and EB3 and the C-terminal partner-binding half of EB1. These cell lines show only mild defects in cell division and microtubule polymerization. However, the length of CAMSAP2-decorated stretches at noncentrosomal microtubule minus ends in these cells is reduced, microtubules are detached from Golgi membranes, and the Golgi complex is more compact. Coorganization of microtubules and Golgi membranes depends on the EB1/EB3–myomegalin complex, which acts as membrane–microtubule tether and counteracts tight clustering of individual Golgi stacks. Disruption of EB1 and EB3 also perturbs cell migration, polarity, and the distribution of focal adhesions. EB1 and EB3 thus affect multiple interphase processes and have a major impact on microtubule minus end organization.

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