Interferon regulatory factor 3 activates p53-dependent cell growth inhibition

Tae Kyung Kim, Joong Seob Lee, Ji Eun Jung, Se Yeong Oh, Sungwook Kwak, Xun Jin, Soo Yeon Lee, Jang Bo Lee, Yong Gu Chung, Young Ki Choi, Seungkwon You, Hyunggee Kim

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Interferon regulatory factor 3 (IRF3) is a transcriptional factor that plays a crucial role in activation of innate immunity and inflammation in response to viral infection. We investigated the biological function of IRF3 overexpressed in somatic cells such as fibroblasts and astrocytes. Similar to overexpression of oncogenic H-ras in the normal human fibroblast, overexpression of IRF3 in human fibroblast BJ cells was shown to decrease cell growth and increase senescence-associated β-galactosidase activity by activating a p53 tumor suppressor. BCNU, a DNA damage agent, further accelerated p53 function and cell death in the IRF3-overexpressed BJ cells compared to control BJ cells, without increased expression of IRF3 target genes. IRF3 failed to activate p53 function and cell growth inhibition in BJ cells downregulating p53 by RNAi-mediated p53 knockdown. Furthermore, enforced expression of IRF3 did not show any effect of cell growth inhibition in astrocytes or embryonic fibroblasts derived from the p53-/- mouse. When compared to control BJ cells, BJ cells which downregulated IRF3 by RNAi-mediated IRF3 knockdown showed extended in vitro life span. Taken together, the present study indicates that IRF3 should be a novel inducer of cell growth inhibition and cellular senescence through activation of p53 tumor suppressor.

Original languageEnglish
Pages (from-to)215-221
Number of pages7
JournalCancer Letters
Volume242
Issue number2
DOIs
Publication statusPublished - 2006 Oct 28

Fingerprint

Interferon Regulatory Factor-3
Cell growth
Growth
Fibroblasts
RNA Interference
Astrocytes
Tumors
Down-Regulation
Chemical activation
Galactosidases
Carmustine
Cell Aging
Interferon-beta
Cell death
Virus Diseases
Helper-Inducer T-Lymphocytes
Innate Immunity
DNA Damage
Neoplasms
Cell Death

Keywords

  • BJ
  • Cell proliferation
  • IFN-β
  • IRF3
  • p53
  • Senescence

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology
  • Oncology

Cite this

Interferon regulatory factor 3 activates p53-dependent cell growth inhibition. / Kim, Tae Kyung; Lee, Joong Seob; Jung, Ji Eun; Oh, Se Yeong; Kwak, Sungwook; Jin, Xun; Lee, Soo Yeon; Lee, Jang Bo; Chung, Yong Gu; Choi, Young Ki; You, Seungkwon; Kim, Hyunggee.

In: Cancer Letters, Vol. 242, No. 2, 28.10.2006, p. 215-221.

Research output: Contribution to journalArticle

Kim, Tae Kyung ; Lee, Joong Seob ; Jung, Ji Eun ; Oh, Se Yeong ; Kwak, Sungwook ; Jin, Xun ; Lee, Soo Yeon ; Lee, Jang Bo ; Chung, Yong Gu ; Choi, Young Ki ; You, Seungkwon ; Kim, Hyunggee. / Interferon regulatory factor 3 activates p53-dependent cell growth inhibition. In: Cancer Letters. 2006 ; Vol. 242, No. 2. pp. 215-221.
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