Harris K F, Chang E, Christensen J B, Imperiale M J
Graduate Program in Cellular and Molecular Biology, Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor 48109-0620, USA.
Dev Biol Stand. 1998;94:81-91.
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.
BK病毒（BKV）是多瘤病毒家族的成员，可持续感染75%-80%的人类。BKV编码一种大T抗原，该抗原负责病毒的转化功能。最近的研究表明，BKV DNA与多种人类肿瘤有关，包括胰岛、脑、泌尿道和卡波西肉瘤。尽管在几种人类肿瘤中检测到了BKV DNA，但尚无明确证据表明其在肿瘤形成中具有致病作用。我们试图表征BKV TAg与细胞肿瘤抑制蛋白（包括p53、pRb、p107和p130）之间的相互作用，以进一步了解BKV转化的分子机制。我们已经表明，BKV TAg可以结合并在功能上抑制p53以及p53介导的对DNA损伤的反应。此外，我们已经表明，尽管与pRb家族成员没有可检测到的相互作用，但低水平的BKV TAg足以诱导游离E2F和血清非依赖性表型。综上所述，这些结果表明，BKV TAg既可以抑制细胞对DNA损伤的反应，又可以诱导增殖，从而可能导致细胞生长控制基因中突变的潜在积累。这些结果表明BKV TAg在人类宿主的细胞转化和肿瘤形成中可能发挥作用。
