Related Experiment Video

Updated: Jul 23, 2025

Reconstitution of Msp1 Extraction Activity with Fully Purified Components
05:52

Reconstitution of Msp1 Extraction Activity with Fully Purified Components

Published on: August 10, 2021

2.5K

MTA1 localizes to the mitotic spindle apparatus and interacts with TPR in spindle assembly checkpoint regulation

Jian Liu1, Hongsheng Xue2, Chunxiao Li3

  • 1Medical Research Center, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, China.

Biochemical and Biophysical Research Communications
|July 19, 2023
PubMed

Insights

Cancer metastasis-associated antigen 1 (MTA1) dynamically localizes to the spindle apparatus and interacts with Translocated Promoter Region (TPR) to regulate the spindle assembly checkpoint (SAC) in cancer cells.

Area of Science:

  • Cell Biology
  • Cancer Research
  • Molecular Oncology

Background:

  • Cancer metastasis-associated antigen 1 (MTA1) has a known cell cycle-dependent distribution and inhibits spindle damage-induced spindle assembly checkpoint (SAC) activation.
  • Detailed subcellular localization and molecular partners of MTA1 in mitotic cancer cells remain unclear.

Purpose of the Study:

  • To elucidate the precise subcellular localization of MTA1 during mitosis in cancer cells.
  • To identify MTA1's interacting partners involved in SAC regulation.
  • To understand MTA1's role in the spindle assembly checkpoint (SAC) and its implications for chromosomal instability (CIN).

Main Methods:

  • Immunofluorescent colocalization analysis of MTA1 and alpha-tubulin in mitotic cancer cells.
  • Assessment of MTA1 expression changes upon spindle damage-induced SAC activation.
  • Time-lapse imaging assays to observe the effect of MTA1 silencing on mitotic progression.
  • Co-immunoprecipitation (co-IP) assays to investigate protein-protein interactions between MTA1, Translocated Promoter Region (TPR), MAD1, and MAD2.

Main Results:

  • MTA1 dynamically localizes to the spindle apparatus throughout mitosis.
  • MTA1 expression is reversibly upregulated upon spindle damage-induced SAC activation.
  • MTA1 silencing delays the metaphase-anaphase transition.
  • MTA1 interacts and colocalizes with TPR on spindle microtubules, an interaction that is attenuated upon SAC activation.
  • No direct interaction was detected between MTA1 and MAD1 or MAD2.

Conclusions:

  • MTA1 plays a dynamic role in SAC regulation by interacting with TPR on spindle microtubules.
  • The MTA1-TPR complex appears to be distinct from the previously described TPR-MAD1/MAD2 complex.
  • Targeting the MTA1-TPR interaction could be a therapeutic strategy to modulate SAC and reduce chromosomal instability (CIN) in cancer.
Keywords:
CancerMTA1Spindle apparatusSpindle assembly checkpointTPR

More Related Videos

Combining Mitotic Cell Synchronization and High Resolution Confocal Microscopy to Study the Role of Multifunctional Cell Cycle Proteins During Mitosis08:33

Combining Mitotic Cell Synchronization and High Resolution Confocal Microscopy to Study the Role of Multifunctional Cell Cycle Proteins During Mitosis

Published on: December 5, 2017

14.3K
Self-Assembly of Microtubule Tactoids08:49

Self-Assembly of Microtubule Tactoids

Published on: June 23, 2022

3.9K

Related Concept Videos

The Spindle Assembly Checkpoint02:19

The Spindle Assembly Checkpoint

The spindle assembly checkpoint is a molecular surveillance mechanism ensuring the fidelity of chromosome segregation during anaphase. The checkpoint monitors the completion of all the prerequisite steps before chromosome segregation to determine whether the segregation process should proceed or be delayed.
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...
3.2K
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
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
Spindle Assembly02:50

Spindle Assembly

Spindle assembly occurs through three, often coexisting, pathways – the centrosome-mediated pathway, the chromatin-mediated pathway, and the microtubule-mediated pathway – collectively contributing to form a robust spindle apparatus.
In most cells, centrosomes are the primary microtubule nucleation centers. In the centrosome-mediated pathway, the G2-prophase transition triggers centrosome maturation and increased microtubule nucleation. Progressive nucleation results in a...
3.7K
Tail-anchoring of Proteins in the ER Membrane01:45

Tail-anchoring of Proteins in the ER Membrane

Tail-anchored, or TA, proteins are estimated to make up to 3-5% of membrane proteins found in the eukaryotic cell. Such proteins have a single transmembrane domain located approximately 30 amino acid residues upstream from the C-terminal end. As a result, the signal recognition particle (SRP) cannot guide a TA protein to the ER membrane for cotranslational insertion. Hence, they are integrated into the ER membrane post-translationally using their C-terminal end as the anchor. TA proteins...
3.1K
DNA Damage can Stall the Cell Cycle02:37

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
9.2K