Oncogenic potential of a dominant negative mutant of interferon regulatory factor 3

Tae Young Kim, Kyoung Hu Lee, Seungwoo Chang, Cheolho Chung, Han Woong Lee, Jeongbin Yim, Tae Kook Kim

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Interferon regulatory factor 3 (IRF3) is activated in response to various environmental stresses including viral infection and DNA-damaging agents. However, the biological function of IRF3 in cell growth is not well understood. We demonstrated that IRF3 markedly inhibited growth and colony formation of cells. IRF3 blocked DNA synthesis and induced apoptosis. Based on this negative control of cell growth by IRF3, we examined whether functional loss of IRF3 may contribute to oncogenic transformation. IRF3 activity was specifically inhibited by expression of its dominant negative mutant. This mutant lacks a portion of the DNA binding domain like IRF3a, an alternative splice form of IRF3 in the cells. This dominant negative inhibition blocked expression of specific IRF3 target genes. Mutant IRF3 efficiently transformed NIH3T3 cells, as demonstrated by anchorage-independent growth in soft agar and tumorigenicity in nude mice. These results imply that IRF3 may function as a tumor suppressor and suggest a possible role for the relative levels of IRF3 and its dominant negative mutant in tumorigenesis.

Original languageEnglish
Pages (from-to)15272-15278
Number of pages7
JournalJournal of Biological Chemistry
Volume278
Issue number17
DOIs
Publication statusPublished - 2003 Apr 25

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this