p202, an interferon-inducible negative regulator of cell growth, is a target of the adenovirus E1A protein.
Studies have revealed that human adenovirus-encoded E1A protein promotes cell proliferation through the targeted interaction with cellular proteins that act as key negative regulators of cell growth. The targets of E1A protein include the retinoblastoma tumor suppressor protein (pRb). Because p202, an interferon (IFN)-inducible murine protein (52-kDa), negatively regulates cell growth in part through the pRb/E2F pathway, we tested whether the p202 is a target of the adenovirus-encoded E1A protein for functional inactivation. Here we report that the expression of E1A protein overcame p202-mediated inhibition of cell growth and this correlated with an alleviation of p202-mediated inhibition of the transcriptional activity of E2F. Furthermore, E1A protein relieved p202-mediated inhibition of the specific DNA-binding activity of E2F complexes, including those containing the pocket proteins. Additionally, the E1A protein bound to p202 both in vitro and in vivo and a deletion of four amino acids in the conserved region 2 (CR2) of E1A protein significantly reduced the binding of E1A to p202. Interestingly, ectopic expression of p202 under reduced serum conditions significantly reduced E1A-mediated apoptosis. Taken together, our observations provide support to the idea that the p202 and adenovirus E1A protein functionally counteract each other and E1A protein targets p202 to promote cell proliferation.
Xin
H
H
Department of Radiation Oncology, Stritch School of Medicine, Loyola University Medical Center, 2160 South First Avenue, Building No. 1, Maywood, Illinois, IL 60153, USA.
D'Souza
S
S
Fang
L
L
Lengyel
P
P
Choubey
D
D
D017500:Adenovirus E1A Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis; D001665:Binding Sites; D002352:Carrier Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D018797:Cell Cycle Proteins; D002455:Cell Division; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors; D050684:E2F Transcription Factors; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007372:Interferons / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology*; D010750:Phosphoproteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000502:physiology; D015533:Transcriptional Activation; D014162:Transfection; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay; D000071857:Tumor Suppressor p53-Binding Protein 1
D017500:Adenovirus E1A Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; C092537:Ifi202b protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; C498301:TP53BP1 protein, human; D014157:Transcription Factors; D000071857:Tumor Suppressor p53-Binding Protein 1; D007372:Interferons