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.
Choubey
D
D
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA.
Li
S J
SJ
Datta
B
B
Gutterman
J U
JU
Lengyel
P
P
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