Related Experiment Video

Updated: Aug 30, 2026

Cytotoxic Efficacy of Photodynamic Therapy in Osteosarcoma Cells In Vitro
08:04

Cytotoxic Efficacy of Photodynamic Therapy in Osteosarcoma Cells In Vitro

Published on: March 18, 2014

Increased mdm-2 expression in a p53-independent manner blocks UV-induced cell cycle arrest and apoptosis in human

Yan Bin Dong1, Hai Liang Yang, Mary Jane Elliott

  • 1Department of Surgery, University of Louisville, James Graham Brown Cancer Center, Louisville, KY 40202, USA.

Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine
|November 12, 2003
PubMed

Insights

MDM-2 overexpression blocks UV-induced apoptosis by inhibiting P53 activity. In this study, high MDM-2 levels prevented P53-mediated cell cycle arrest and apoptosis, even after DNA damage.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • DNA damage triggers p53 protein accumulation, crucial for cell cycle arrest and apoptosis.
  • The p53 and MDM-2 proteins form a feedback loop where p53 activates MDM-2 transcription, and MDM-2 inhibits p53 activity and promotes its degradation.

Purpose of the Study:

  • To investigate the interaction between endogenous MDM-2 and p53 in an MDM-2 overexpressing cell line after UV-induced DNA damage.
  • To understand the role of MDM-2 overexpression in cellular response to UV radiation.

Main Methods:

  • Utilized a human osteosarcoma cell line (OsACL) with wild-type p53 and MDM-2 overexpression.
  • Assessed p53 levels, transcriptional activity (using CAT assays), MDM-2 mRNA and protein levels (Northern blot), and cell cycle progression (cell cycle analysis).
  • Investigated the effect of MDM-2 downregulation using anti-sense MDM-2 plasmid transfection.

Main Results:

  • UV treatment increased p53 levels in OsACL cells, but p53 remained transcriptionally inactive.
  • MDM-2 levels significantly increased post-UV irradiation, correlating with elevated MDM-2 mRNA, suggesting increased transcription.
  • OsACL cells exhibited resistance to UV-induced apoptosis, which was restored upon MDM-2 downregulation.

Conclusions:

  • MDM-2 overexpression inhibits UV-induced cell cycle arrest and apoptosis by suppressing p53 transcriptional activity.
  • The observed increase in MDM-2 expression following UV irradiation in OsACL cells appears to be regulated by p53-independent mechanisms.

More Related Videos

Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols12:02

Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols

Published on: June 6, 2017

Chemical-Induced Skin Carcinogenesis Model Using Dimethylbenz[a]Anthracene and 12-O-Tetradecanoyl Phorbol-13-Acetate (DMBA-TPA)04:12

Chemical-Induced Skin Carcinogenesis Model Using Dimethylbenz[a]Anthracene and 12-O-Tetradecanoyl Phorbol-13-Acetate (DMBA-TPA)

Published on: December 19, 2019

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 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...
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.
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
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...