An IFN regulatory factor-2 DNA-binding domain dominant negative mutant exhibits altered cell growth and gene expression

Y. R. Rubinstein, P. H. Driggers, V. V. Ogryzko, A. M. Thornton, K. Ozato, C. H. Pontzer

Research output: Contribution to journalArticlepeer-review

Abstract

In order to study interferon regulatory factor (IRF) family mediation of cell growth regulation, we established U937 cell lines stably transfected with a truncated form of IRF-2 lacking the transcriptional repressor domain. The truncated IRF-2 contained the DNA binding domain (DBD) and bound the ISRE. Phenotypically, the IRF-2 DBD transfectants exhibited reduced cell growth, altered morphology and increased cell death. Consistent with alterations in growth characteristics, the IRF-2 DBD transfectants constitutively expressed higher levels of the cyclin dependent kinase inhibitor p21(WAF1/Cip1) than did control clones. The level of p21(WAF1/Cip1) expression was positively correlated with the level of DBD expressed, as well as with the level of growth inhibition in these clones. DBD expression also correlated with expression of other members of the growth regulatory complex, cyclin dependent kinase 2 and cyclin A, but not proliferating cell nuclear antigen. These results imply active repression by IRF-2 to keep p21(WAF1/Cip1) transcriptionally silent.

Original languageEnglish (US)
Pages (from-to)1411-1418
Number of pages8
JournalOncogene
Volume19
Issue number11
DOIs
StatePublished - Mar 9 2000

Keywords

  • Cell growth
  • Interferon
  • Interferon regulatory factor

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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