Transcriptional blockade induces p53-dependent apoptosis associated with translocation of p53 to mitochondria

Yoshimi Arima, Masayuki Nitta, Shinji Kuninaka, Dongwei Zhang, Toshiyoshi Fujiwara, Yoichi Taya, Mitsuyoshi Nakao, Hideyuki Saya

研究成果: Article査読

123 被引用数 (Scopus)

抄録

The tumor suppressor p53 functions as a transcriptional activator to induce cell cycle arrest and apoptosis in response to BNA damage. Although p53 was also shown to mediate apoptosis in a manner independent of its transactivation activity, the mechanism and conditions that trigger such cell death have remained largely unknown. We have now shown that inhibition of RNA polymerase II-mediated transcription by α-amanitin or RNA interference induced p53-dependent apoptosis. Inhibition of pol II-mediated transcription resulted in down-regulation of p21Cip1, which was caused by both transcriptional suppression and protein degradation, despite eliciting p53 accumulation, allowing the cells to progress into S phase and then to undergo apoptosis. This cell death did not require the transcription of p53 target genes and was preceded by translocation of the accumulated p53 to mitochondria. Our data thus suggested that blockade of pol II-mediated transcription induced p53 accumulation in mitochondria and was the critical factor for eliciting p53-dependent but transcription-independent apoptosis.

本文言語English
ページ(範囲)19166-19176
ページ数11
ジャーナルJournal of Biological Chemistry
280
19
DOI
出版ステータスPublished - 2005 5 13
外部発表はい

ASJC Scopus subject areas

  • 生化学
  • 分子生物学
  • 細胞生物学

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