Lack of p53 delays apoptosis, but increases ubiquitinated inclusions, in proteasomal inhibitor-treated cultured cortical neurons

Paula Dietrich, Hardy J. Rideout, Qiaohong Wang, Leonidas Stefanis

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Proteasomal dysfunction may contribute to neurodegenerative diseases; however, its effects on primary neurons are largely unknown. We have previously reported that pharmacological proteasomal inhibition leads to apoptosis and cytoplasmic ubiquitinated inclusions in primary rat cortical neurons. In cell lines the transcription factor p53 is regulated by the proteasome and in some cases it mediates death following proteasomal inhibition. It is unclear, however, if this is the case in primary neurons. Here we show in proteasome inhibitor-treated cortical neurons an early increase of p53 levels, accompanied by nuclear translocation. At later time points p53 is found sequestered within ubiquitinated inclusions. Compared to controls, p53-deficient mouse neurons show delayed apoptosis, but increased numbers of inclusions, likely secondary to enhanced survival. We conclude that p53 plays a role in cortical neuron apoptosis induced by proteasomal inhibition and, despite the fact that it localizes to inclusions, it is not necessary for their formation.

Original languageEnglish (US)
Pages (from-to)430-441
Number of pages12
JournalMolecular and Cellular Neuroscience
Volume24
Issue number2
DOIs
StatePublished - Jan 1 2003

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Apoptosis
Neurons
Proteasome Inhibitors
Inclusion Bodies
Proteasome Endopeptidase Complex
Neurodegenerative Diseases
Transcription Factors
Pharmacology
Cell Line

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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Lack of p53 delays apoptosis, but increases ubiquitinated inclusions, in proteasomal inhibitor-treated cultured cortical neurons. / Dietrich, Paula; Rideout, Hardy J.; Wang, Qiaohong; Stefanis, Leonidas.

In: Molecular and Cellular Neuroscience, Vol. 24, No. 2, 01.01.2003, p. 430-441.

Research output: Contribution to journalArticle

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