Related Experiment Video

Updated: May 28, 2026

Knockdown of FAM83A to Verify Its Role in Cervical Cancer Cell Growth and Cisplatin Sensitivity
04:20

Knockdown of FAM83A to Verify Its Role in Cervical Cancer Cell Growth and Cisplatin Sensitivity

Published on: February 9, 2024

MG132 inhibition of proteasome blocks apoptosis induced by severe DNA damage

Ling Zhang1, Jennifer J Hu, Feng Gong

  • 1Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL, USA.

Cell Cycle (Georgetown, Tex.)
|October 28, 2011
PubMed

Insights

The 26S proteasome, crucial for protein degradation, surprisingly promotes apoptosis following severe UV damage by degrading p53. Inhibiting the proteasome blocks this cell death pathway.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • The 26S proteasome degrades ubiquitinated proteins, playing a role in cellular regulation.
  • Proteasome inhibitors are explored as chemotherapeutic agents due to their ability to induce apoptosis.

Purpose of the Study:

  • To investigate the role of the 26S proteasome in DNA damage-induced apoptosis.
  • To elucidate the mechanism of p53 regulation by the proteasome under UV irradiation.

Main Methods:

  • Cell treatment with MG132 (proteasome inhibitor) and varying doses of UV irradiation.
  • Analysis of apoptosis, p53 stabilization, and p21/WAF1 expression.

Main Results:

  • MG132 treatment blocked DNA damage-induced apoptosis, correlating with p53 stabilization and p21/WAF1 upregulation.
  • High-dose UV irradiation induced robust apoptosis associated with rapid p53 degradation, unlike low-dose UV which caused p53 stabilization.
  • Severe UV damage triggers proteasomal degradation of p53.

Conclusions:

  • The 26S proteasome plays a critical role in promoting apoptosis following high-dose UV irradiation.
  • Proteasome-mediated p53 degradation is a key event in severe UV-induced cell death.
  • The proteasome's function in apoptosis is context-dependent, influenced by the extent of cellular damage.

More Related Videos

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs10:44

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

Published on: May 15, 2019

Related Concept Videos

The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
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 daughter...
DNA Damage can Stall the Cell Cycle02:36

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...
DNA Damage Can Stall the Cell Cycle02:36

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...
Cellular Injury V: Apoptosis and Autophagy01:22

Cellular Injury V: Apoptosis and Autophagy

Cells respond to damage and stress through highly coordinated processes that decide whether they survive or undergo controlled self-destruction. Two major pathways involved in this regulation are apoptosis, a type of programmed cell death, and autophagy, a survival mechanism that helps cells adapt to adverse conditions.ApoptosisApoptosis removes aged or injured cells to maintain tissue balance. During this process, the cell shrinks, chromatin condenses and fragments, and membrane-bound...
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.