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

Research output: Contribution to journalArticle

115 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)19166-19176
Number of pages11
JournalJournal of Biological Chemistry
Volume280
Issue number19
DOIs
Publication statusPublished - 2005 May 13
Externally publishedYes

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Mitochondria
Transcription
Apoptosis
Cell death
Cell Death
Amanitins
RNA Polymerase II
p53 Genes
RNA Interference
Cell Cycle Checkpoints
S Phase
Transcriptional Activation
Proteolysis
Tumors
Down-Regulation
Genes
Cells
RNA
Degradation
Neoplasms

ASJC Scopus subject areas

  • Biochemistry

Cite this

Transcriptional blockade induces p53-dependent apoptosis associated with translocation of p53 to mitochondria. / Arima, Yoshimi; Nitta, Masayuki; Kuninaka, Shinji; Zhang, Dongwei; Fujiwara, Toshiyoshi; Taya, Yoichi; Nakao, Mitsuyoshi; Saya, Hideyuki.

In: Journal of Biological Chemistry, Vol. 280, No. 19, 13.05.2005, p. 19166-19176.

Research output: Contribution to journalArticle

Arima, Yoshimi ; Nitta, Masayuki ; Kuninaka, Shinji ; Zhang, Dongwei ; Fujiwara, Toshiyoshi ; Taya, Yoichi ; Nakao, Mitsuyoshi ; Saya, Hideyuki. / Transcriptional blockade induces p53-dependent apoptosis associated with translocation of p53 to mitochondria. In: Journal of Biological Chemistry. 2005 ; Vol. 280, No. 19. pp. 19166-19176.
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AU - Taya, Yoichi

AU - Nakao, Mitsuyoshi

AU - Saya, Hideyuki

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