Related Experiment Video

Updated: Sep 14, 2025

Examining Proteasome Assembly with Recombinant Archaeal Proteasomes and Nondenaturing PAGE: The Case for a Combined Approach
09:57

Examining Proteasome Assembly with Recombinant Archaeal Proteasomes and Nondenaturing PAGE: The Case for a Combined Approach

Published on: December 17, 2016

6.7K

19S proteasome loss regulates mitotic spindle assembly through a ubiquitin-independent degradation mechanism

Océane Marescal1, Iain M Cheeseman1

  • 1Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.

Cell Reports
|July 24, 2025
PubMed

Insights

Loss of the 19S proteasome particle, not other subunits, causes monopolar spindles by enabling ubiquitin-independent degradation of the KIF11 motor protein, disrupting mitosis.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Proteasome Function

Background:

  • The 26S proteasome, composed of 19S regulatory and 20S catalytic subunits, degrades ubiquitinated proteins.
  • Proteasome subunit loss can lead to distinct cellular phenotypes, impacting processes like mitosis.

Purpose of the Study:

  • To investigate the specific role of 19S proteasome subunits in cellular phenotypes, particularly spindle assembly during mitosis.
  • To elucidate the mechanism behind the monopolar spindle phenotype observed in proteasome subunit knockouts.

Main Methods:

  • Utilizing knockout strategies for different proteasome subcomplexes.
  • Analyzing cellular phenotypes, focusing on spindle assembly during mitosis.
  • Investigating the degradation pathways of key proteins, including the kinesin motor protein KIF11.

Main Results:

  • Depletion of 19S proteasome lid (PSMD) proteins specifically prevents bipolar spindle assembly, unlike other proteasome subunit knockouts.
  • The monopolar spindle phenotype in PSMD knockouts results from aberrant, ubiquitin-independent degradation of KIF11 via the 20S proteasome.
  • Loss of 19S proteins leads to altered spindle forces due to KIF11 degradation, causing the unique monopolar phenotype.

Conclusions:

  • The 19S proteasome particle plays a crucial role in ensuring proper spindle formation during mitosis.
  • The 19S particle restrains ubiquitin-independent degradation pathways, preventing aberrant KIF11 loss and maintaining mitotic integrity.
Keywords:
CP: Cell biologydegradationkinesinmitosisproteasomespindleubiquitin

More Related Videos

Monitoring of Ubiquitin-proteasome Activity in Living Cells Using a Degron dgn-destabilized Green Fluorescent Protein GFP-based Reporter Protein10:25

Monitoring of Ubiquitin-proteasome Activity in Living Cells Using a Degron dgn-destabilized Green Fluorescent Protein GFP-based Reporter Protein

Published on: November 10, 2012

16.8K
Studying Proteolysis of Cyclin B at the Single Cell Level in Whole Cell Populations10:54

Studying Proteolysis of Cyclin B at the Single Cell Level in Whole Cell Populations

Published on: September 17, 2012

10.6K

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...
1.2K
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...
3.3K
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...
974
Separation of Sister Chromatids02:17

Separation of Sister Chromatids

At the transition from prophase to metaphase, there is a reduction in cohesion along the chromosomal arms, resulting in the resolution of sister chromatids. However, residual cohesin connections remain to hold the sister chromatids together until the transition from metaphase to anaphase. The residual connection prevents any premature separation of sister chromatids, blocking the risks of aneuploidy within the daughter cells.
At the onset of anaphase, separase, a proteolytic enzyme, is...
3.8K
Anaphase Promoting Complex00:50

Anaphase Promoting Complex

The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
2.9K
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...
5.3K