BK virus as a potential co-factor in human cancer.
BK virus (BKV) is a member of the polyomavirus family that persistently infects 75-80% of the human population. BKV encodes a large T antigen which is responsible for the transforming functions of the virus. Recent studies have shown an association of BKV DNA with a variety of human tumours including pancreatic islet, brain, urinary tract and Kaposi's sarcoma. Despite the detection of BKV DNA in several human tumours, there is no clear evidence for a causative role in tumour formation. We have sought to characterize the interactions of BKV TAg with cellular tumour suppressor proteins including p53, pRb, p107, and p130 in an attempt to further understand the molecular mechanisms of transformation by BKV. We have shown that BKV TAg can bind to and functionally inhibit p53 and the p53-mediated response to DNA damage. Additionally, we have shown that low levels of BKV TAg are sufficient to induce free E2F and a serum-independent phenotype despite the absence of detectable interactions with pRb family members. Taken together, these results suggest that BKV TAg can both inhibit the cellular response to DNA damage and induce proliferation, allowing for potential accumulation of mutations in cellular growth control genes. These results suggest a possible role for BKV TAg in cellular transformation and tumour formation in the human host.
Graduate Program in Cellular and Molecular Biology, Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor 48109-0620, USA.
K F
KF
Harris
E
E
Chang
J B
JB
Christensen
M J
MJ
Imperiale
D000952:Antigens, Polyomavirus Transforming / Q000378:metabolism; D001739:BK Virus / Q000235:genetics / Q000472:pathogenicity*; D002471:Cell Transformation, Neoplastic; D004279:DNA, Viral / Q000737:chemistry; D006801:Humans; D027601:Polyomavirus Infections / Q000150:complications*; D014412:Tumor Virus Infections / Q000150:complications*
D000952:Antigens, Polyomavirus Transforming; D004279:DNA, Viral