Related Experiment Video

Updated: Jun 2, 2025

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics
06:00

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics

Published on: May 14, 2016

11.0K

Proteasome inhibition induces microtubule-dependent changes in nuclear morphology

Sourabh Sengupta1, Abdullah Bashar Sami1, Jesse C Gatlin1

  • 1Department of Molecular Biology, University of Wyoming, Laramie, WY 82071, USA.

Iscience
|January 15, 2025
PubMed

Insights

Proteasome inhibition acutely alters nuclear shape and stability by affecting microtubules. Increased Tubulin GCP6 protein accumulation drives these nuclear changes, impacting cell integrity.

Area of Science:

  • Cell Biology
  • Proteostasis and Nuclear Morphology

Background:

  • Disrupted proteostasis and altered nuclear morphology are linked to diseases like cancer and neurodegeneration.
  • Understanding the direct mechanisms linking proteostasis to nuclear morphology is challenging due to confounding cellular processes.

Purpose of the Study:

  • To investigate the direct impact of proteostasis disruption on nuclear morphology.
  • To elucidate the molecular mechanisms underlying proteasome inhibition-induced nuclear changes.

Main Methods:

  • Utilized *Xenopus* egg extract system to isolate effects of proteostasis disruption without transcription, translation, or cell cycle progression.
  • Applied proteasome inhibition and proteomic analysis.
  • Investigated the role of Tubulin GCP6 (Gamma-tubulin complex protein 6) and microtubule dynamics.
  • Confirmed findings in HeLa cells.

Main Results:

  • Proteasome inhibition induced rapid, microtubule-dependent changes in nuclear morphology and stability.
  • Microtubule dynamics and organization were altered following proteasome inhibition.
  • Proteomic analysis revealed increased abundance of microtubule nucleator TubGCP6.
  • Depletion of TubGCP6 partially restored normal nuclear morphology.

Conclusions:

  • Accumulation of TubGCP6 alters microtubule dynamics near the nucleus.
  • Altered microtubule dynamics generate forces that deform the nucleus, impacting its morphology and integrity.
  • This provides a direct mechanistic link between proteostasis and nuclear structural integrity.
Keywords:
Biological sciencesCell biologyFunctional aspects of cell biology

More Related Videos

Analysis of Translation Initiation During Stress Conditions by Polysome Profiling10:59

Analysis of Translation Initiation During Stress Conditions by Polysome Profiling

Published on: May 19, 2014

18.2K
Quantifying Subcellular Ubiquitin-proteasome Activity in the Rodent Brain09:25

Quantifying Subcellular Ubiquitin-proteasome Activity in the Rodent Brain

Published on: May 21, 2019

6.7K

Related Concept Videos

The Proteasome01:13

The Proteasome

Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
807
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...
2.0K
Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.4K
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...
2.6K
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...
1.9K
The Proteasome Structure01:17

The Proteasome Structure

The ubiquitin-proteasome pathway is a well-known mechanism utilized by eukaryotic cells to remove cytoplasmic proteins that are misfolded, damaged, or no longer needed. In this pathway, the protein that needs to be eliminated undergoes a process called ubiquitination, where a chain of ubiquitin molecules is attached to the 48th lysine residue of the target protein. This ubiquitin modification helps the proteasome distinguish between a target protein and a healthy protein.
The proteasome is an...
687