Xie, RonglinVan Wijnen, Andre J.van der Meijden, Caroline M. J.Stein, Janet L.Stein, Gary S.2022-08-232022-08-232002-05-012008-06-18Cancer Res. 2002 May 1;62(9):2510-5.0008-5472 (Print)11980642https://hdl.handle.net/20.500.14038/40802The IFN regulatory factor-2 (IRF-2) oncoprotein controls the cell cycle-dependent expression of histone H4 genes during S phase and may function as a component of an E2F-independent mechanism to regulate cell growth. To investigate the role of IRF-2 in control of cell proliferation, we have constructed a stable FDC-P1 cell line (F2) in which expression of IRF-2 is doxycycline (DOX)-inducible, and a control cell line (F0). Both the F2 and F0 cell lines were synchronized in the G1 phase by isoleucine deprivation, and IRF-2 was induced by DOX on release of cells from the cell cycle block. Flow cytometric analyses indicated that forced expression of IRF-2 has limited effects on cell cycle progression before the first mitosis. However, continued cell growth in the presence of elevated IRF-2 levels results in polyploidy (>4n) or genomic disintegration (<2n) and cell death. Western blot analyses revealed that the levels of the cell cycle regulatory proteins cyclin B1 and the cyclin-dependent kinase (CDK)-inhibitory protein p27 are selectively increased. These changes occur concomitant with a significant elevation in the levels of the FAS-L protein, which is the ligand of the FAS (Apo1/CD95) receptor. We also found a subtle change in the ratio of the apoptosis-promoting Bax protein and the antiapoptotic Bcl-2 protein. Hence, IRF-2 induces a cell death response involving the Fas/FasL apoptotic pathway in FDC-P1 cells. Our data suggest that the IRF-2 oncoprotein regulates a critical cell cycle checkpoint that controls progression through G2 and mitosis in FDC-P1 hematopoietic progenitor cells.en-USAnimalsAntigens, CD95ApoptosisCell DeathCell DivisionDNA-Binding ProteinsFas Ligand ProteinG1 PhaseGene Expression RegulationHistonesInterferon Regulatory Factor-2Membrane GlycoproteinsMiceMyeloid Progenitor Cells*Polyploidy*Repressor ProteinsS Phase*Transcription FactorsUp-RegulationCancer BiologyCell and Developmental BiologyMedical Cell BiologyOncologyForced expression of the interferon regulatory factor 2 oncoprotein causes polyploidy and cell death in FDC-P1 myeloid hematopoietic progenitor cellsJournal Articlehttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1360&context=oapubs&unstamped=1https://escholarship.umassmed.edu/oapubs/361533071oapubs/361