Related Experiment Video

Updated: Dec 29, 2025

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs
10:44

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs

Published on: May 15, 2019

13.6K

MARCH5-dependent degradation of MCL1/NOXA complexes defines susceptibility to antimitotic drug treatment

Manuel D Haschka1, Gerlinde Karbon1, Claudia Soratroi1

  • 1Institute for Developmental Immunology, Biocenter, Medical University of Innsbruck, 6020, Innsbruck, Austria.

Cell Death and Differentiation
|February 5, 2020
PubMed

Insights

Inhibiting MARCH5 E3-ligase prevents cancer cell death evasion by stabilizing NOXA protein. This sensitizes cells to microtubule targeting agents, enhancing anti-cancer therapy effectiveness.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • Microtubule targeting agents (MTAs) induce apoptosis in cancer cells by arresting mitosis.
  • MCL-1 degradation, regulated by NOXA, is critical for MTA-induced apoptosis timing.
  • Cancer cells can evade apoptosis through mitotic slippage.

Purpose of the Study:

  • To investigate the role of the E3-ligase MARCH5 in regulating MCL1/NOXA complexes.
  • To determine if MARCH5 inhibition can sensitize cancer cells to MTAs.

Main Methods:

  • Utilized cell culture models and biochemical assays.
  • Investigated protein-protein interactions and degradation pathways.
  • Assessed cellular responses to MTA treatment and MARCH5 inhibition.

Main Results:

  • MARCH5 regulates MCL1/NOXA protein complex levels in both steady-state and mitotic arrest.
  • MARCH5 inhibition leads to NOXA accumulation and sensitizes cells to MTAs.
  • Inhibition of MARCH5 primes cancer cells for cell death in the G1 phase after potential mitotic slippage.

Conclusions:

  • MARCH5 is a key regulator of MCL1/NOXA complexes and cellular response to mitotic stress.
  • Inhibiting MARCH5 enhances cancer cell sensitivity to MTAs.
  • Targeting MARCH5 represents a potential strategy to improve antimitotic cancer therapy.

More Related Videos

Pooled shRNA Library Screening to Identify Factors that Modulate a Drug Resistance Phenotype14:51

Pooled shRNA Library Screening to Identify Factors that Modulate a Drug Resistance Phenotype

Published on: June 17, 2022

3.5K
Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence10:09

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence

Published on: January 7, 2019

8.6K

Related Concept Videos

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...
3.5K
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...
3.3K
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.6K
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...
5.0K
Electron Transport Chain: Complex I and II01:46

Electron Transport Chain: Complex I and II

The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
18.2K
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...
2.5K