Interferon regulatory factor 5, a novel mediator of cell cycle arrest and cell death.
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 G(2)-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.
Barnes
Betsy J
BJ
Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, 1650 Orleans Street, Baltimore, MD 21231, USA. barnebe@jhmi.edu
Kellum
Merrill J
MJ
Pinder
Karen E
KE
Frisancho
J Augusto
JA
Pitha
Paula M
PM
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000096:biosynthesis / Q000235:genetics; D002453:Cell Cycle / Q000502:physiology*; D002455:Cell Division / Q000502:physiology; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D005260:Female; D016195:G2 Phase / Q000502:physiology; D045325:HCT116 Cells; D006801:Humans; D050839:Interferon Regulatory Factor-7; D050835:Interferon Regulatory Factors; D007938:Leukemia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008819:Mice, Nude; D008938:Mitosis / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein
C494772:BAK1 protein, human; C494826:BAX protein, human; C494773:Bak1 protein, mouse; C494827:Bax protein, mouse; C493956:CDKN1A protein, human; C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004268:DNA-Binding Proteins; C431713:IRF5 protein, human; C494234:IRF7 protein, human; D050839:Interferon Regulatory Factor-7; D050835:Interferon Regulatory Factors; C494235:Irf7 protein, mouse; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; C505530:CASP8 protein, human; C506433:CASP9 protein, human; C505526:Casp8 protein, mouse; C506434:Casp9 protein, mouse; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases