Apoptosis by Par-4 in cancer and neurodegenerative diseases

Nadia El-Guendy, Vivek M. Rangnekar

Research output: Contribution to journalReview articlepeer-review

114 Scopus citations

Abstract

Prostate apoptosis response-4 (par-4) is a pro-apoptotic gene identified in prostate cancer cells undergoing apoptosis. Par-4 protein, which contains a leucine zipper domain at the carboxy-terminus, functions as a transcriptional repressor in the nucleus. Par-4 selectively induces apoptosis in androgen-independent prostate cancer cells and Ras-transformed cells but not in androgen-dependent prostate cancer cells or normal cells. Cells that are resistant to apoptosis by Par-4 alone, however, are greatly sensitized by Par-4 to the action of other pro-apoptotic insults such as growth factor withdrawal, tumor necrosis factor, ionizing radiation, intracellular calcium elevation, or those involved in neurodegenerative diseases such as Alzheimer's, Parkinson's, Huntington's, and stroke. Apoptosis induction by Par-4 involves a complex mechanism that requires activation of the Fas death receptor signaling pathway and coparallel inhibition of cell survival NF-κB transcription activity. The unique ability of Par-4 to induce apoptosis in cancer cells but not normal cells and the ability of Par-4 antisense or dominant-negative mutant to abrogate apoptosis in neurodegenerative disease paradigms makes it an appealing candidate for molecular therapy of cancer and neuronal diseases.

Original languageEnglish
Pages (from-to)51-66
Number of pages16
JournalExperimental Cell Research
Volume283
Issue number1
DOIs
StatePublished - Feb 1 2003

Bibliographical note

Funding Information:
This work was supported by NIH research grants CA60872 and CA84511. We thank Sushma Gurumurthy for a critical reading of the review.

Keywords

  • Alzheimer's disease
  • Apoptosis
  • Cancer
  • Neurodegenerative diseases
  • Par-4
  • Prostate apoptosis response-4

ASJC Scopus subject areas

  • Cell Biology

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