Related Experiment Video

Updated: Jul 7, 2026

Procedure and Key Optimization Strategies for an Automated Capillary Electrophoretic-based Immunoassay Method
09:32

Procedure and Key Optimization Strategies for an Automated Capillary Electrophoretic-based Immunoassay Method

Published on: September 10, 2017

Induction of p21 by p65 in p53 null cells treated with Doxorubicin

Shenglin Ma1, Juanjuan Tang, Jianguo Feng

  • 1Zhejiang Tumor Hospital, Banshanqiao,Hangzhou, Zhejiang Province, China.

Biochimica Et Biophysica Acta
|February 14, 2008
PubMed

Insights

Nuclear factor kappa B (NFkappaB)/p65 influences cancer cell death by regulating p21 expression. This study reveals p65 is crucial for p53-dependent cell death, impacting p21 levels and chemotherapy response.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cellular Signaling

Background:

  • Nuclear factor kappa B (NFkappaB)/p65 is a transcription factor with dual roles in cell survival and death.
  • Previous research established p21's role in suppressing cell death through cyclin-dependent kinase (CDK) inhibition.

Purpose of the Study:

  • To investigate the role of NFkappaB/p65 in doxorubicin (DOX)-induced cell death in HCT116 cells.
  • To elucidate the regulatory relationship between p53, p65, and p21 expression in response to chemotherapy.

Main Methods:

  • Knockdown of p65 using IkappaBSR or p65 siRNA in HCT116 cells with varying p53 statuses.
  • Assessment of doxorubicin (DOX) cytotoxicity and p21 expression levels.
  • Analysis of p65 binding to the p21 promoter via chromatin immunoprecipitation.

Main Results:

  • p65 knockdown decreased DOX cytotoxicity in p53-positive cells, correlating with increased p21 induction.
  • p65 downregulation enhanced DOX cytotoxicity in p53-null cells, linked to decreased p21 expression.
  • Evidence suggests p65 directly binds the p21 promoter in p53-null cells.

Conclusions:

  • p65 activity is required for p53-dependent cell death by limiting p53-induced p21 expression.
  • A novel mechanism exists where p53 and p65 mutually repress p21 induction, potentially through competition for p300/CBP coactivators.
  • p21 acts as a bridge in the transcriptional crosstalk between p53 and p65, influencing chemoresistance.

More Related Videos

Evaluating the Effect of SASP Factors on the Proliferation of Cancer Cells Using a Comparative Analysis of Three Distinct Methodologies08:57

Evaluating the Effect of SASP Factors on the Proliferation of Cancer Cells Using a Comparative Analysis of Three Distinct Methodologies

Published on: September 19, 2025

Induction and Validation of Cellular Senescence in Primary Human Cells08:18

Induction and Validation of Cellular Senescence in Primary Human Cells

Published on: June 20, 2018

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...