Evidence for dysregulation of cell cycle by human polyomavirus, JCV, late auxiliary protein.
The late region of the human neurotropic JC virus encodes a 71 amino acid protein, named Agnoprotein, whose biological function remains elusive. Here we demonstrate that in the absence of other viral proteins, expression of Agnoprotein can inhibit cell growth by deregulating cell progression through the cell cycle stages. Cells with constitutive expression of Agnoprotein were largely accumulated at the G2/M stage and that decline in the activity of cyclins A and B is observed in these cells. Agnoprotein showed the ability to augment p21 promoter activity in transient transfection assay and a noticeable increase in the level of p21 is detected in cells continuously expressing Agnoprotein. Results from binding studies revealed the interaction of Agnoprotein with p53 through the N-terminal of the Agnoprotein spanning residues 1-36. Co-expression of p53 and Agnoprotein further stimulated transcription of the p21 promoter. Thus, the interaction of p53 and Agnoprotein can lead to a higher level of p21 expression and suppression of cell cycle progression during the cell cycle.
Darbinyan
Armine
A
Center for Neurovirology and Cancer Biology, College of Science and Technology, Temple University, 1900 North 12th Street, 015-96, Philadelphia, Pennsylvania, PA 19122, USA.
Darbinian
Nune
N
Safak
Mahmut
M
Radhakrishnan
Sujatha
S
Giordano
Antonio
A
Khalili
Kamel
K
D016475:3T3 Cells / Q000378:metabolism / Q000821:virology; D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism; D015153:Blotting, Western; D002453:Cell Cycle; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000378:metabolism; D005434:Flow Cytometry; D015967:Gene Expression Regulation, Viral; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D007577:JC Virus / Q000502:physiology*; D008164:Luminescent Proteins / Q000378:metabolism; D051379:Mice; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000502:physiology; D011494:Protein Kinases / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014764:Viral Proteins / Q000502:physiology*; D054334:Viral Regulatory and Accessory Proteins; D000086082:Viroporin Proteins
D001426:Bacterial Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D017931:DNA Primers; D004791:Enzyme Inhibitors; D005982:Glutathione Transferase; D008164:Luminescent Proteins; D011494:Protein Kinases; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins; C493956:CDKN1A protein, human; C493957:Cdkn1a protein, mouse; C042559:agnoprotein, polyomavirus; D000086082:Viroporin Proteins; C054562:yellow fluorescent protein, Bacteria; C102333:histone H1 kinase