Related Experiment Video

Updated: Aug 3, 2026

Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes
15:43

Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes

Published on: January 7, 2013

Regulation of p53 target gene expression by cisplatin-induced extracellular signal-regulated kinase

R D DeHaan1, E M Yazlovitskaya, D L Persons

  • 1Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City 66160-7232, USA.

Cancer Chemotherapy and Pharmacology
|January 5, 2002
PubMed

Insights

The extracellular signal-regulated kinase (ERK) pathway regulates key proteins involved in DNA repair and cell cycle control following cisplatin chemotherapy. Inhibiting ERK activity reduces the expression of these essential proteins, impacting cellular response to DNA damage.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Signaling

Background:

  • Cisplatin is a DNA damage-inducing chemotherapeutic agent.
  • The extracellular signal-regulated kinase (ERK) pathway is activated by cisplatin.
  • ERK pathway inhibition enhances cisplatin sensitivity and is required for p53 accumulation.

Purpose of the Study:

  • To investigate the effect of cisplatin-induced ERK activation on p53-targeted genes.
  • To determine the role of ERK in regulating genes crucial for DNA damage response.

Main Methods:

  • Utilized the A2780 ovarian carcinoma cell line.
  • Administered cisplatin to induce DNA damage and ERK activation.
  • Inhibited ERK activity using PD98059.
  • Analyzed the expression of p53-targeted genes (Bax, Bcl-2, Bcl-x1, Cyclin G, Gadd45, p21WAF1, Mdm2) via quantitative analysis.

Main Results:

  • Cisplatin upregulated p21WAF1, Gadd45, and Mdm2 expression.
  • Cisplatin did not affect the expression of Bax, Bcl-2, Bcl-x1, or Cyclin G.
  • Inhibition of ERK activity by PD98059 decreased the levels of p21WAF1, Gadd45, and Mdm2.

Conclusions:

  • ERK activity plays a regulatory role in the cisplatin DNA damage response.
  • ERK influences the expression of cell cycle control (p21WAF1, Gadd45), DNA repair (Gadd45), and p53-regulatory (Mdm2) proteins.

More Related Videos

Procedure and Key Optimization Strategies for an Automated Capillary Electrophoretic-based Immunoassay Method09:32

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

Published on: September 10, 2017

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

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.
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...
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...
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...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...