CDC20-Mediated hnRNPU Ubiquitination Regulates Chromatin Condensation and Anti-Cancer Drug Response

Related Experiment Video

Updated: Sep 1, 2025

A Screening Method for Identification of Heterochromatin-Promoting Drugs Using Drosophila
06:22

A Screening Method for Identification of Heterochromatin-Promoting Drugs Using Drosophila

Published on: March 12, 2020

6.1K

Cindy Wavelet-Vermuse1, Olena Odnokoz1, Yifan Xue2

  • 1Department of Pharmacology and Chemical Biology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USA.

Cancers
|August 12, 2022
PubMed

Insights

Cell division cycle 20 (CDC20) regulates chromatin condensation by ubiquitylating hnRNPU, impacting cancer progression and drug resistance. This CDC20-hnRNPU axis is crucial for tumor development.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • Cell division cycle 20 (CDC20) is a key regulator of the cell cycle.
  • CDC20 is implicated in cancer development and drug resistance.
  • The precise mechanisms of CDC20 in cellular drug response are not fully understood.

Purpose of the Study:

  • To investigate the molecular mechanisms of CDC20 in regulating cellular drug response.
  • To identify CDC20 interacting partners in breast cancer cells.
  • To elucidate the role of the CDC20-hnRNPU interaction in tumor progression and drug resistance.

Main Methods:

  • Affinity purification coupled with mass spectrometry to identify CDC20 interactome.
  • Co-immunoprecipitation and immunostaining to validate protein interactions.
  • DAPI and H2B-mCherry staining to assess nuclear size and chromatin condensation.
  • CCK-8 and clonogenic assays to evaluate tumor progression and drug resistance.

Main Results:

  • hnRNPU was identified as a novel binding partner of CDC20.
  • CDC20-mediated ubiquitination of hnRNPU enhances its interaction with CTCF and cohesin complex.
  • The CDC20-hnRNPU interaction modulates chromatin condensation, nuclear size, and impacts tumor progression.
  • Dysregulation of the CDC20-hnRNPU axis correlates with increased tumor progression and drug resistance.

Conclusions:

  • CDC20-mediated ubiquitination of hnRNPU is a critical mechanism for modulating chromatin condensation.
  • The CDC20-hnRNPU axis plays a significant role in breast cancer progression and acquired drug resistance.
  • Targeting the CDC20-hnRNPU pathway may offer novel therapeutic strategies for cancer treatment.
Keywords:
CDC20chromatin condensationcohesin complexdrug resistancehnRNPUmitotic slippage

More Related Videos

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics06:00

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

Published on: May 14, 2016

11.1K
In Vitro Ubiquitination and Deubiquitination Assays of Nucleosomal Histones11:36

In Vitro Ubiquitination and Deubiquitination Assays of Nucleosomal Histones

Published on: July 25, 2019

10.9K

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.6K
Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
7.0K
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
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...
9.3K
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
35.8K
Epigenetic Regulation01:37

Epigenetic Regulation

Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
3.1K