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Interferon Regulatory Factor 5, a Novel Mediator of Cell Cycle Arrest and Cell Death¹

Department of Oncology, Sidney Kimmel Comprehensive Cancer Center [B. J. B., M. J. K., K. E. P., J. A. F., P. M. P.] and Department of Molecular Biology and Genetics [P. M. P.], The Johns Hopkins University School of Medicine, Baltimore, Maryland 21231

We have previously shown a critical role for IFN regulatory factor 5 (IRF-5) in the innate immune response to virus infection. For the first time, we now show that although IRF-5 is a direct target of p53, its cell cycle regulatory and proapoptotic effects are p53 independent. IRF-5 inhibits both in vitro and in vivo B-cell lymphoma tumor growth in the absence of wild-type p53. The molecular mechanism(s) of IRF-5-mediated growth inhibition is associated with a G₂-M cell cycle arrest and modulation of growth regulatory and proapoptotic genes, including p21, Bak, DAP kinase 2, and Bax. Taken together, these data indicate that although IRF-5 is a downstream target of p53, its growth inhibitory and proapoptotic effects are independent of p53.

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