Related Experiment Video

Updated: Aug 8, 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

Modulation of nitric oxide-evoked apoptosis by the p53-downstream target p21(WAF1/CIP1)

F Yang1, A von Knethen, B Brüne

  • 1University of Erlangen-Nürnberg, Faculty of Medicine, Department of Medicine IV, Erlangen, Germany.

Journal of Leukocyte Biology
|December 29, 2000
PubMed

Insights

Excess nitric oxide (NO) impacts cell cycle and apoptosis. This study shows p21(WAF1/CIP1) is a key mediator, regulated by p53, influencing macrophage response to NO.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • Nitric oxide (NO) is an inflammatory mediator that can affect cell cycle progression and induce cell death.
  • The protein p21(WAF1/CIP1) and the tumor suppressor p53 are implicated in regulating these cellular processes.

Purpose of the Study:

  • To investigate the specific role of p21(WAF1/CIP1) in mediating the effects of NO on cell cycle arrest and apoptosis.
  • To elucidate the relationship between p53 and p21(WAF1/CIP1) in the context of NO-induced cellular responses in macrophages.

Main Methods:

  • Stable transfection of macrophages with antisense p21(WAF1/CIP1)-encoding plasmids.
  • Exposure of transfected and parent macrophages to nitric oxide.
  • Analysis of p53 and p21(WAF1/CIP1) expression levels.
  • Flow cytometry to assess cell cycle distribution (G1 and sub-G1 phases) and apoptosis.

Main Results:

  • Inhibition of p21(WAF1/CIP1) expression attenuated NO-induced G1 cell-cycle arrest and sensitized cells to apoptosis.
  • Elimination of p53 function led to reduced expression of both p53 and p21(WAF1/CIP1), abrogated cell cycle arrest, and prevented apoptosis.
  • These findings indicate p21(WAF1/CIP1) acts downstream of p53 in NO-mediated macrophage responses.

Conclusions:

  • p21(WAF1/CIP1) is a critical downstream target of p53 in macrophages responding to nitric oxide.
  • The p53-p21(WAF1/CIP1) pathway modulates macrophage sensitivity to the immune-modulatory effects of NO, influencing cell cycle arrest and apoptosis.

More Related Videos

Yeast As a Chassis for Developing Functional Assays to Study Human P5314:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

Knockdown of FAM83A to Verify Its Role in Cervical Cancer Cell Growth and Cisplatin Sensitivity04:20

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

Published on: February 9, 2024

Related Concept Videos

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.
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...
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
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...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
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...