BK virus large T antigen: interactions with the retinoblastoma family of tumor suppressor proteins and effects on cellular growth control.
BK virus (BKV) is a polyomavirus which infects a large percentage of the human population. It is a potent transforming agent and is tumorigenic in rodents. BKV DNA has also been found in human brain, pancreatic islet, and urinary tract tumors, implicating this virus in neoplastic processes. BKV T antigen (TAg) is highly homologous to simian virus 40 TAg, particularly in regions required for mitogenic stimulation and binding to tumor suppressor proteins, The experiments presented in this report show that BKV TAg can bind the tumor suppressor protein p53. BKV TAg also has the ability to bind to members of the retinoblastoma (pRb) family of tumor suppressor proteins both in vivo and in vitro. However, these interactions are detected only when large amounts of total protein are used, because the levels of BKV TAg normally produced from viral promoter-enhancer elements are too low to bind a significant amount of the pRb family proteins in the cell. The low levels of BKV TAg produced by the viral promoter elements are sufficient to affect the levels and the phosphorylation patterns of these proteins and to induce serum-independent growth in these cells. Additional events, however, are required for full transformation. These data further support the notion that BKV TAg can affect cellular growth control mechanisms and may in fact be involved in neoplastic processes.
Harris
K F
KF
Graduate Program in Cellular and Molecular Biology, University of Michigan Medical School, Ann Arbor 48109-0620, USA.
Christensen
J B
JB
Imperiale
M J
MJ
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000378:metabolism / Q000502:physiology*; D001739:BK Virus / Q000276:immunology / Q000502:physiology*; D002455:Cell Division; D002460:Cell Line; D002472:Cell Transformation, Viral / Q000502:physiology*; D002522:Chlorocebus aethiops; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D011485:Protein Binding; D011506:Proteins; D016160:Retinoblastoma Protein / Q000378:metabolism*; D050720:Retinoblastoma-Like Protein p107; D050717:Retinoblastoma-Like Protein p130; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D000952:Antigens, Polyomavirus Transforming; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011506:Proteins; C493844:RBL1 protein, human; C493837:RBL2 protein, human; D016160:Retinoblastoma Protein; D050720:Retinoblastoma-Like Protein p107; D050717:Retinoblastoma-Like Protein p130; D016159:Tumor Suppressor Protein p53