Inhibition of E2F-mediated transcription by p202.
Many of the antimicrobial, immunomodulatory and cell growth inhibitory activities of the interferons are mediated by interferon-inducible proteins. Earlier we characterized an interferon-inducible murine protein, p202, whose expression in transfected cells inhibits cell proliferation and which can form a complex with retinoblastoma protein (pRb). Here we report that in transfected cells expression of p202 inhibits E2F-stimulated transcription of a reporter gene and of endogenous genes. Inhibition of the transcriptional activity of E2F by p202 does not depend on fully functional pRb and is correlated with inhibition of the sequence-specific DNA binding of E2F. p202 interacts with the transcription factor E2F (E2F-1/DP-1) in vitro and in vivo. Inhibition of E2F activity by p202 may contribute to growth inhibition by the interferons.
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA.
D
D
Choubey
S J
SJ
Li
B
B
Datta
J U
JU
Gutterman
P
P
Lengyel
D000818:Animals; D002352:Carrier Proteins / Q000494:pharmacology*; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D007372:Interferons / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D009687:Nuclear Proteins / Q000494:pharmacology*; D010750:Phosphoproteins / Q000494:pharmacology*; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects*; D014407:Tumor Cells, Cultured; D000071857:Tumor Suppressor p53-Binding Protein 1
C533431:Arid4a protein, mouse; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; C493754:E2f1 protein, mouse; C092537:Ifi202b protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D056465:Retinoblastoma-Binding Protein 1; C498301:TP53BP1 protein, human; D050680:Transcription Factor DP1; D014157:Transcription Factors; D000071857:Tumor Suppressor p53-Binding Protein 1; D004247:DNA; D007372:Interferons