Related Experiment Video

Updated: Aug 19, 2025

Live Imaging to Study Microtubule Dynamic Instability in Taxane-resistant Breast Cancers
06:02

Live Imaging to Study Microtubule Dynamic Instability in Taxane-resistant Breast Cancers

Published on: February 20, 2017

7.6K

α-Tubulin detyrosination links the suppression of MCAK activity with taxol cytotoxicity

Danilo Lopes1,2, Alexandre L Seabra1,2, Bernardo Orr1,2

  • 1Chromosome Instability & Dynamics Group, i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.

The Journal of Cell Biology
|December 2, 2022
PubMed

Insights

High levels of acetylated alpha-tubulin may predict cancer cell response to taxol. Increased detyrosinated alpha-tubulin enhances taxol

Area of Science:

  • Biochemistry
  • Cell Biology
  • Cancer Research

Background:

  • Microtubules are crucial for cell division and are targeted by cancer drugs.
  • Alpha/beta-tubulin posttranslational modifications (PTMs) create microtubule diversity.
  • The role of tubulin PTMs in cancer drug resistance is not fully understood.

Purpose of the Study:

  • To investigate the
  • cancer tubulin code
  • and its impact on cancer cell resistance to microtubule-targeting drugs.
  • To determine if specific tubulin PTMs, such as acetylation and detyrosination, influence taxol efficacy.
  • To explore the relationship between tubulin PTMs, microtubule dynamics, and cancer cell death.

Main Methods:

  • Analysis of the NCI-60 cancer cell panel to assess tubulin PTMs.
  • Experimental manipulation of α-tubulin detyrosination and MCAK levels.
  • Assessment of taxol-induced cytotoxicity, cell death, and spindle morphology.

Main Results:

  • Acetylated α-tubulin levels correlated with taxol-induced cytotoxicity but were not essential.
  • Increased α-tubulin detyrosination and/or MCAK depletion enhanced taxol efficacy, promoting cell death.
  • Increased detyrosinated α-tubulin aggravated taxol-induced spindle multipolarity.

Conclusions:

  • High α-tubulin acetylation may serve as a biomarker for taxol response in cancer cells.
  • A mechanistic link exists between α-tubulin detyrosination, suppressed MCAK activity, and enhanced taxol cytotoxicity.
  • This suggests a role for detyrosination in promoting chromosome missegregation and cell death, independent of spindle defects.

More Related Videos

Generation of Prostate Cancer Cell Models of Resistance to the Anti-mitotic Agent Docetaxel06:44

Generation of Prostate Cancer Cell Models of Resistance to the Anti-mitotic Agent Docetaxel

Published on: September 8, 2017

13.5K
Quantitative Microtubule Fractionation Technique to Separate Stable Microtubules, Labile Microtubules, and Free Tubulin in Mouse Tissues07:21

Quantitative Microtubule Fractionation Technique to Separate Stable Microtubules, Labile Microtubules, and Free Tubulin in Mouse Tissues

Published on: November 17, 2023

2.1K

Related Concept Videos

Drugs that Stabilize Microtubules01:15

Drugs that Stabilize Microtubules

Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...
2.1K
Drugs that Destabilize Microtubules01:10

Drugs that Destabilize Microtubules

Microtubules are dynamic structures and can be regulated by microtubule targeting agents (MTAs). Microtubule destabilizing drugs are a class of MTAs that destabilize and prevent microtubules' polymerization. Both natural and synthetic chemicals can be found under this class of drugs. Vincristine and vinblastine, two vinca alkaloids, and colchicine were among the first to be discovered. These drugs can affect cells in various ways, either by inducing a change in cell morphology, preventing...
2.0K
Destabilization of Microtubules01:45

Destabilization of Microtubules

The destabilization of microtubules can occur during different stages of the microtubule lifecycle, such as nucleation or elongation. It can take place at either end of the microtubule or in the microtubule lattices as a whole. The lifespan of individual microtubules within a cell varies according to the cell type and stage of the cell cycle. During interphase, the lifespan of the microtubule is about 30 minutes, while during cell division, it is about 15 minutes. In axonal microtubules of...
2.8K
Microtubule Instability02:17

Microtubule Instability

Microtubules are hollow cylindrical filaments having a diameter of approximately 25 nm and a length that varies from 200 nm to 25 μm. GTP-bound tubulin subunits form αβ-heterodimers for microtubule assembly. These core building blocks interact longitudinally, polymerizing into protofilaments. The protofilaments then interact with one another through lateral bonding forces to form stable cylindrical microtubules. These cylindrical filaments are dynamic as they undergo repeated...
5.2K
Microtubule Associated Proteins (MAPs)01:42

Microtubule Associated Proteins (MAPs)

Microtubule function and architecture are regulated by an array of specialized proteins called microtubule-associated proteins or MAPs. These proteins are widespread across different organisms and have conserved protein motifs, like the multi-TOG domain for tubulin binding found in the CLASP family of MAPs. Some MAPs are lineage-specific based on their conserved domains. Their functions depend upon the cytoskeletal architecture and cell type they are located within. In-plant cells, a specific...
4.4K
Allosteric Proteins-ATCase01:19

Allosteric Proteins-ATCase

Binding sites linkages can regulate a protein's function.  For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to  N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
5.8K