P202, an interferon-inducible protein, inhibits E2F1-mediated apoptosis in prostate cancer cells.
p202, an interferon (IFN) inducible protein, is a phosphonuclear protein involved in the regulation of cell cycle, apoptosis, and differentiation. E2F1 belongs to the E2F family of proteins that are important cell cycle regulators in promoting cell growth. On the other hand, the deregulated expression of E2F1 also triggers apoptosis independent of p53 status. It has been well documented that p202 is able to inhibit cell growth by binding to E2F1 and abolishing the E2F1-mediated transcriptional activation of S-phase genes. However, it is not known whether E2F1-mediated apoptosis can be counteracted by p202 expression. Here, we show that E2F1-mediated apoptosis induced by the infection of an E2F1-expressing adenoviral vector (Ad-E2F1) was greatly diminished in p202-expressing prostate cancer cells. The E2F1-mediated caspase-3 activation was also reduced in p202-expressing cells infected with Ad-E2F1. Since caspase-3 is one of the E2F1 transcriptional targets, this result is consistent with the ability of p202 to inhibit the transcriptional activity of E2F1. Therefore, our results suggest a possible link between the IFN and E2F pathways in regulating apoptosis.
Yan
Duen-Hwa
DH
Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center and Graduate School of Biomedical Sciences, 1515 Holcombe Blvd., Houston, TX 77030, USA. dyan@mdanderson.org
Abramian
Aram
A
Li
Zheng
Z
Ding
Yi
Y
Wen
Yong
Y
Liu
Ta-Jen
TJ
Hunt
Kelly
K
D017209:Apoptosis; D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism* / Q000502:physiology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D018797:Cell Cycle Proteins; D002455:Cell Division; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D004789:Enzyme Activation; D005434:Flow Cytometry; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D010750:Phosphoproteins / Q000378:metabolism* / Q000502:physiology; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D013997:Time Factors; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D000071857:Tumor Suppressor p53-Binding Protein 1
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; C498301:TP53BP1 protein, human; D014157:Transcription Factors; D000071857:Tumor Suppressor p53-Binding Protein 1; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases