Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

Regulation of p53 expression by the RAS-MAP kinase pathway.

M L Agarwal1, C V Ramana, M Hamilton

  • 1Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio, OH 44195, USA.

Oncogene
|June 23, 2001
PubMed
Summary
This summary is machine-generated.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Letter to the Editor: Immediate interlocking nailing versus external fixation followed by delayed interlocking nailing for Gustilo type IIIB open tibial fractures.

Journal of orthopaedic surgery (Hong Kong)·2007
Same author

Pulsed degenerate optical parametric oscillator based on a nonlinear-fiber Sagnac interferometer.

Optics letters·2007
Same author

Comparison of the incidence and severity of cough induced by sufentanil and fentanyl: a prospective, randomised, double-blind study.

Anaesthesia·2007
Same author

Comparative evaluation of myolaxin and EMLA cream for attenuation of venous cannulation pain: a prospective, randomised, double blind study.

Anaesthesia and intensive care·2007
Same author

HOpe for contrast-induced acute kidney injury.

Kidney international·2007
Same author

Voided urinary cytology in bladder cancer: is it time to review the indications?

Urology·2007
Same journal

Correction: SIRT7 activates p53 by enhancing PCAF-mediated MDM2 degradation to arrest the cell cycle.

Oncogene·2026
Same journal

Correction: Liver-specific SIRT1 knockout-induced hyperglycemia promotes spontaneous lung adenocarcinomas through HSF1-MDM2.

Oncogene·2026
Same journal

Correction: 6-Phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 is essential for p53-null cancer cells.

Oncogene·2026
Same journal

Matrix stiffness drives HCC invasion and metastasis via interfering with TRIM21-mediated SCD1 ubiquitination.

Oncogene·2026
Same journal

DNA methylation-mediated silencing of STAT5A drives breast cancer metastasis via dual regulation of EMT and immunosuppressive microenvironment.

Oncogene·2026
Same journal

LncRNA IRENA promotes peripheral T-cell lymphoma progression through scaffolding ARHGEF1 and FMNL1 to modulate RHOA GTPase/MAPK signaling.

Oncogene·2026
See all related articles

Mitogen-activated protein (MAP) kinase pathways regulate p53 levels by controlling p53 mRNA expression. This study identifies a defect in MAP kinase signaling in a fibrosarcoma cell line, impacting p53 and p21 expression.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Cancer Research

Background:

  • Cross-talk exists between MAP kinase and p53 pathways.
  • The precise mechanisms regulating p53 protein levels in response to MAP kinase signaling are not fully elucidated.
  • Ras-activated signaling pathways are implicated in cancer development.

Purpose of the Study:

  • To investigate the relationship between MAP kinase activity and p53 expression.
  • To identify molecular defects affecting p53 regulation in cancer cells.
  • To understand how activated ras signaling influences p53 and downstream targets.

Main Methods:

  • Isolation and characterization of a mutant cell line (AP14) with defective p53 expression.
  • Analysis of p53 mRNA and protein levels.

Related Experiment Videos

  • Assessment of MAP kinase (ERK1/ERK2) phosphorylation and activity.
  • Gene expression analysis of p53-regulated genes (p21).
  • Functional rescue experiments involving gene overexpression and phosphatase inhibition.

    • Main Results:

    • The AP14 mutant cell line exhibited significantly reduced p53 mRNA and protein levels compared to parental HT1080 fibrosarcoma cells.
    • AP14 cells showed decreased phosphorylation and activity of ERK1 and ERK2 MAP kinases.
    • Overexpression of ERK2 in AP14 cells restored MAP kinase activity and p53 expression.
    • Treatment with a phosphatase inhibitor (orthovanadate) elevated both MAP kinase activity and p53 levels in AP14 cells.
    • Expression of p21, a p53 target gene, paralleled p53 levels.
    • Activated ras signaling increased p53 mRNA, while MEK inhibition reduced p53 and p21 protein levels in wild-type cells.

    Conclusions:

    • MAP kinase-dependent pathways play a crucial role in regulating p53 levels.
    • The regulation of p53 levels by MAP kinases occurs at the level of p53 mRNA expression.
    • These findings provide insights into the molecular mechanisms linking ras signaling, MAP kinase activation, and p53 pathway modulation in cancer.