The effects of a mutant p53 protein on the proliferation and differentiation of PC12 rat phaeochromocytoma cells

Zsolt Fábián, Mónika Vecsernyés, Marianna Pap, J. Szeberényi

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

PC12 rat phaeochromocytoma cells show neuronal differentiation upon NGF treatment. NGF induces prolonged activation of the Ras/Raf/MEK/ERK pathway in which the 42/44 kDa mitogen-activated protein kinases (MAPKs), ERK 1 and 2 are thought to be the key mediators of the differentiation signals. Activation of ERKs leads to the increased transcription of early response genes resulting in cell cycle arrest. Upon NGF treatment the p53 protein, the most commonly mutated tumor suppressor in human cancers, translocates to the nucleus and may play a role in the mediation of NGF-induced cell cycle arrest and neuronal differentiation. Here we demonstrate that in PC12 cells expressing both wild-type and V143A mutant p53 proteins (p143p53PC12 cells), p53-mediated biological responses are critically influenced. p143p53PC12 cells are not able to cease their proliferation and begin their neuronal differentiation program upon NGF treatment. The presence of mutant p53 also reduces the DNA-binding activity of endogenous p53 and disturbs the regulatory machinery of p53 including both the phosphorylation of ERK1/2, p38 and SAPK/JNK MAP kinases and itself.

Original languageEnglish
Pages (from-to)1431-1441
Number of pages11
JournalJournal of Cellular Biochemistry
Volume99
Issue number5
DOIs
Publication statusPublished - Dec 1 2006

Fingerprint

Pheochromocytoma
Nerve Growth Factor
Mutant Proteins
Rats
Cells
Cell Cycle Checkpoints
Proteins
Chemical activation
Genetic Transcription
MAP Kinase Kinase 4
Phosphorylation
MAP Kinase Signaling System
Mitogen-Activated Protein Kinase 1
PC12 Cells
Mitogen-Activated Protein Kinase Kinases
p38 Mitogen-Activated Protein Kinases
Transcription
Mitogen-Activated Protein Kinases
Machinery
Tumors

Keywords

  • ERK pathway
  • NGF
  • Stress signaling
  • V143A p53 mutation

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

Cite this

The effects of a mutant p53 protein on the proliferation and differentiation of PC12 rat phaeochromocytoma cells. / Fábián, Zsolt; Vecsernyés, Mónika; Pap, Marianna; Szeberényi, J.

In: Journal of Cellular Biochemistry, Vol. 99, No. 5, 01.12.2006, p. 1431-1441.

Research output: Contribution to journalArticle

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